''Mycoplasma pneumoniae'' is a very small
bacterium
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
in the class
Mollicutes
Mollicutes is a class of bacteria distinguished by the absence of a cell wall. The word "Mollicutes" is derived from the Latin ''mollis'' (meaning "soft" or "pliable"), and ''cutis'' (meaning "skin"). Individuals are very small, typically only 0. ...
. It is a human pathogen that causes the disease
mycoplasma pneumonia
''Mycoplasma'' pneumonia (also known as "walking pneumonia") is a form of bacterial pneumonia caused by the bacterial species ''Mycoplasma pneumoniae''. It is also known as PPLO, which is an acronym for Pleuro Pneumonia Like Organism.
Pathophysiol ...
, a form of
atypical
''Atypical'' is an American comedy-drama television series created by Robia Rashid for Netflix. It focuses on the life of 18-year-old Sam Gardner ( Keir Gilchrist), who is on the autism spectrum. The first season was released on August 11, 201 ...
bacterial pneumonia
Bacterial pneumonia is a type of pneumonia caused by bacterial infection.
Types
Gram-positive
''Streptococcus pneumoniae'' () is the most common bacterial cause of pneumonia in all age groups except newborn infants. ''Streptococcus pneumoniae'' ...
related to
cold agglutinin disease
Cold agglutinin disease (CAD) is a rare disease, rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below , dir ...
. ''M. pneumoniae'' is characterized by the absence of a
peptidoglycan cell wall
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ...
and resulting resistance to many
antibacterial agents. The persistence of ''M. pneumoniae'' infections even after treatment is associated with its ability to mimic
host cell
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
surface composition.
Discovery and history
In 1898, Nocard and Roux isolated an agent assumed to be the cause of cattle pneumonia and named it ''microbe de la peripneumonie''
Microorganisms from other sources, having properties similar to the pleuropneumonia organism (PPO) of cattle, soon came to be known as
pleuropneumonia-like organisms (PPLO), but their true nature remained unknown.
Many PPLO were later proven to be the cause of pneumonias and arthritis in several lower animals.
In 1944, Monroe Eaton had used embryonated chicken eggs to cultivate an agent thought to be the cause of human primary atypical pneumonia (PAP), commonly known as "walking pneumonia."
This unknown organism became known as the "Eaton agent". At that time, Eaton's use of embryonated eggs, then used for cultivating viruses, supported the idea that the Eaton agent was a virus. Yet it was known that PAP was amenable to treatment with
broad-spectrum antibiotic
A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial inf ...
s, making a viral etiology suspect.
Robert Chanock, a researcher from the
NIH
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
who was studying the Eaton agent as a virus, visited the
Wistar Institute
The Wistar Institute () is an independent, nonprofit research institution in biomedical science, with expertise in oncology, immunology, infectious disease and vaccine research. Located on the campus of the University of Pennsylvania, Wistar was ...
in
Philadelphia
Philadelphia, often called Philly, is the largest city in the Commonwealth of Pennsylvania, the sixth-largest city in the U.S., the second-largest city in both the Northeast megalopolis and Mid-Atlantic regions after New York City. Sinc ...
in 1961 to obtain a cell culture of a normal human cell strain developed by
Leonard Hayflick
Leonard Hayflick (born 20 May 1928) is a Professor of Anatomy at the UCSF School of Medicine, and was Professor of Medical Microbiology at Stanford University School of Medicine. He is a past president of the Gerontological Society of America and ...
. This cell strain was known to be exquisitely sensitive to isolate and grow human viruses. Chanock told Hayflick of his research on the Eaton agent, and his belief that its viral nature was questionable. Although Hayflick knew little about the current research on this agent, his doctoral dissertation had been done on animal diseases caused by PPLO. Hayflick knew that many lower animals suffered from pneumonias caused by PPLOs (later to be termed ''mycoplasmas''). Hayflick reasoned that the Eaton agent might be a mycoplasma, and not a virus.
Chanock had never heard of mycoplasmas, and at Hayflick’s request sent him egg yolk containing the Eaton agent.
[
:
]
Using a novel
agar and fluid medium formulation he had devised,
Hayflick isolated a unique mycoplasma from the egg yolk. This was soon proven by Chanock and Hayflick to be the causative agent of PAP.
When this discovery became known to Dr. Emmy Klieneberger-Nobel of the Lister Institute in London, the world’s leading authority on these organisms, she suggested that the organism be named ''Mycoplasma hayflickiae''.
Hayflick demurred in favor of ''Mycoplasma pneumoniae''.
This smallest free-living microorganism was the first to be isolated and proven to be the cause of a human disease. For his discovery, Hayflick was presented with the Presidential Award by the International Organization of Mycoplasmology. The inverted microscope under which Hayflick discovered ''Mycoplasma pneumoniae'' is kept by the
Smithsonian Institution
The Smithsonian Institution ( ), or simply the Smithsonian, is a group of museums and education and research centers, the largest such complex in the world, created by the U.S. government "for the increase and diffusion of knowledge". Founded ...
.
Taxonomy and classification
The term
mycoplasma
''Mycoplasma'' is a genus of bacteria that, like the other members of the class ''Mollicutes'', lack a cell wall around their cell membranes. Peptidoglycan (murein) is absent. This characteristic makes them naturally resistant to antibiotics ...
( meaning fungus, and , meaning formed) is derived from the
fungal
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...
-like growth of some mycoplasma species.
[ The mycoplasmas were classified as ]Mollicutes
Mollicutes is a class of bacteria distinguished by the absence of a cell wall. The word "Mollicutes" is derived from the Latin ''mollis'' (meaning "soft" or "pliable"), and ''cutis'' (meaning "skin"). Individuals are very small, typically only 0. ...
(“mollis”, meaning soft and “cutis”, meaning skin) in 1960 due to their small size and genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
, lack of cell wall
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...
, low G+C content
G, or g, is the seventh letter in the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is ''gee'' (pronounced ), plural ''gees''.
History
Th ...
and unusual nutritional
Nutrition is the biochemical and physiological process by which an organism uses food to support its life. It provides organisms with nutrients, which can be metabolized to create energy and chemical structures. Failure to obtain sufficien ...
needs. ''M. pneumoniae'' has also been designated as an arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
nonferment
Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...
ing species. Mycoplasmas are further classified by the sequence composition of 16s rRNA. All mycoplasmas of the ''pneumoniae'' group possess similar 16s rRNA variations unique to the group, of which ''M. pneumoniae'' has a 6.3% variation in the conserved regions, that suggest mycoplasmas formed by degenerative evolution from the gram-positive
In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall.
Gram-positive bacte ...
eubacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
l group that includes ''bacilli
Bacilli is a taxonomic class of bacteria that includes two orders, Bacillales and Lactobacillales, which contain several well-known pathogens such as ''Bacillus anthracis'' (the cause of anthrax). ''Bacilli'' are almost exclusively gram-positi ...
'', '' streptococci'', and ''lactobacilli
The ''Lactobacillaceae'' are a family of lactic acid bacteria. It is the only family in the lactic acid bacteria which includes homofermentative and heterofermentative organisms; in the ''Lactobacillaceae,'' the pathway used for hexose fermentati ...
''. ''M. pneumoniae'' is a member of the family Mycoplasmataceae
Mycoplasmataceae is a family of bacteria in the order Mycoplasmatales. This family consists of the genera '' Mycoplasma'' and '' Ureaplasma''.
In 1967, the order Mycoplasmatales was incorporated into the class Mollicutes. Many species are sexua ...
and order Mycoplasmatales
Mycoplasmataceae is a family of bacteria in the order Mycoplasmatales. This family consists of the genera ''Mycoplasma'' and '' Ureaplasma''.
In 1967, the order Mycoplasmatales was incorporated into the class Mollicutes. Many species are sexual ...
.[
]
Cell biology
Mycoplasmas, which are among the smallest self-replicating organisms, are parasitic
Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has c ...
species that lack a cell wall and periplasmic space
The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found tha ...
, have reduced genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
s, and limited metabolic
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
activity. ''Mycoplasma pneumoniae'' cells have an elongated shape that is approximately 0.1–0.2 µm (100-200 nm) in width and 1-2 µm (1000-2000 nm) in length. The extremely small cell size means they are incapable of being examined by light microscopy
Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...
; a stereomicroscope
The stereo, stereoscopic or dissecting microscope is an optical microscope variant designed for low magnification observation of a sample, typically using light reflected from the surface of an object rather than transmitted through it. The instr ...
is required for viewing the morphology
Morphology, from the Greek and meaning "study of shape", may refer to:
Disciplines
* Morphology (archaeology), study of the shapes or forms of artifacts
* Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies ...
of ''M. pneumoniae'' colonies
In modern parlance, a colony is a territory subject to a form of foreign rule. Though dominated by the foreign colonizers, colonies remain separate from the administration of the original country of the colonizers, the '' metropolitan state'' ...
, which are usually less than 100 µm in length.[ The inability to synthesize a ]peptidoglycan cell wall
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ...
is due to the absence of gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s encoding its formation and results in an increased importance in maintenance of osmotic
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...
stability to avoid desiccation
Desiccation () is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic (attracts and holds water) substance that induces or sustains such a state in its local vicinity in a moderately sealed container.
...
.[ The lack of a cell wall also calls for increased support of the ]cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
(reinforced with sterols), which includes a rigid cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
composed of an intricate protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
network and, potentially, an extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
capsule to facilitate adherence to the host cell
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
.[ ''M. pneumoniae'' are the only ]bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l cells that possess cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
in their cell membrane (obtained from the host) and possess more genes that encode for membrane lipoprotein
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...
variations than other mycoplasmas, which are thought to be associated with its parasitic lifestyle. ''M. pneumoniae'' cells also possess an attachment organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
, which is used in the gliding motility Gliding motility is a type of translocation used by microorganisms that is independent of propulsive structures such as flagella, pili, and fimbriae. Gliding allows microorganisms to travel along the surface of low aqueous films. The mechanisms of ...
of the organism by an unknown mechanism.[
]
Genomics and metabolic reconstruction
Sequencing
In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succ ...
of the ''M. pneumoniae'' genome in 1996 revealed it is 816,394 bp in size. The genome contains 687 genes that encode for proteins, of which about 56.6% code for essential metabolic enzymes
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
; notably those involved in glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
and organic acid
An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids, whose acidity is associated with their carboxyl group –COOH. Sulfonic acids, containing the group –SO2OH, are rel ...
fermentation
Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...
. ''M. pneumoniae'' is consequently very susceptible to loss of enzymatic function by gene mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
s, as the only buffering systems against functional loss by point mutations are for maintenance of the pentose phosphate pathway
The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt and the HMP Shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-pho ...
and nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
metabolism. Loss of function in other pathways is suggested to be compensated by host cell metabolism. In addition to the potential for loss of pathway function, the reduced genome of ''M. pneumoniae'' outright lacks a number of pathways, including the TCA cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins ...
, respiratory electron transport chain, and biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
pathways for amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
, fatty acids
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
, cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
and purines
Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines ...
and pyrimidines
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...
. These limitations make ''M. pneumoniae'' dependent upon import systems to acquire essential building blocks from their host or the environment that cannot be obtained through glycolytic pathways. Along with energy costly protein and RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
production, a large portion of energy metabolism is exerted to maintain proton gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and th ...
s (up to 80%) due to the high surface area to volume ratio
The surface-area-to-volume ratio, also called the surface-to-volume ratio and variously denoted sa/vol or SA:V, is the amount of surface area per unit volume of an object or collection of objects.
SA:V is an important concept in science and engi ...
of ''M. pneumoniae'' cells. Only 12 – 29% of energy metabolism is directed at cell growth
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...
, which is unusually low for bacterial cells, and is thought to be an adaptation
In biology, adaptation has three related meanings. Firstly, it is the dynamic evolutionary process of natural selection that fits organisms to their environment, enhancing their evolutionary fitness. Secondly, it is a state reached by the po ...
of its parasitic lifestyle.
Alternative genetic code
Unlike other bacteria, ''M. pneumoniae'' uses the codon
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
UGA to code for tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
rather than using it as a stop codon.
Comparative metabolomics
''Mycoplasma pneumoniae'' has a reduced metabolome
The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The smal ...
in comparison to other bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l species. This means that the pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
has much fewer metabolic reactions in comparison to other bacterial species such as '' B.subtilis'' and ''Escherichia coli''.
Since ''Mycoplasma pneuomiae'' has a reduced genome, it has a smaller number of overall paths and metabolic enzymes, which contributes to its more linear metabolome. A linear metabolome causes ''Mycoplasma pneumoniae'' to be less adaptable to external factors. Additionally, since ''Mycoplasma pneumoniae'' is a reduced genome, the majority of its metabolic enzymes are essential. This is in contrast to another model organism, ''Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', in which only 15% of its metabolic enzymes are essential. In summary, the linear topology of ''Mycoplasma pneumonaie's'' metabolome leads to reduced efficiency in its metabolic reactions, but still maintains similar levels of metabolite concentrations, cellular energetics, adaptability, and global gene expression.
The table above depicts the mean path length for the metabolomes of ''M. pneumonaie'', ''E. coli'', '' L. lactis'', and ''B. subtilis''. This number describes, essentially, the mean number of reactions that occur in the metabolome. ''Mycoplasma pneuomonaie'', on average, has a high number of reactions per path within its metabolome in comparison to other model bacterial species.
One effect of ''Mycoplasma pneumoniae''’s unique metabolome is its longer duplication time. It takes the pathogen significantly more time to duplicate on average compared to other model organism bacteria. This may be due to the fact that ''Mycoplasma pneumoniae’s'' metabolome is less efficient than that of ''Escherichia coli''.
The metabolome of ''Mycoplasma pneumoniae'' can also be informative in analyzing its pathogenesis. Extensive study of the metabolic network of this organism has led to the identification of biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
s that can potentially reveal the presence of the extensive complications the bacteria can cause. Metabolomics is increasingly being used as a useful tool for the verification of biomarkers of infectious pathogens.
Host and reproduction
''Mycoplasma pneumoniae'' grows exclusively by parasitizing
Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted structurally to this way of lif ...
mammals. Reproduction
Reproduction (or procreation or breeding) is the biological process by which new individual organisms – "offspring" – are produced from their "parent" or parents. Reproduction is a fundamental feature of all known life; each individual or ...
, therefore, is dependent upon attachment to a host cell. According to Waite and Talkington, specialized reproduction occurs by “binary fission
Binary may refer to:
Science and technology Mathematics
* Binary number, a representation of numbers using only two digits (0 and 1)
* Binary function, a function that takes two arguments
* Binary operation, a mathematical operation that t ...
, temporally linked with duplication of its attachment organelle, which migrates to the opposite pole of the cell during replication and before nucleoid separation”.[ ]Mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
that affect the formation of the attachment organelle not only hinder motility
Motility is the ability of an organism to move independently, using metabolic energy.
Definitions
Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
and cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
, but also reduce the ability of ''M. pneumoniae'' cells to adhere to the host cell.
Pathogenicity
''Mycoplasma pneumoniae'' parasitizes the respiratory tract
The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa.
Air is breathed in through the nose to th ...
epithelium
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
of humans.[ Adherence to the respiratory epithelial cells is thought to occur via the attachment organelle, followed by evasion of ]host
A host is a person responsible for guests at an event or for providing hospitality during it.
Host may also refer to:
Places
* Host, Pennsylvania, a village in Berks County
People
*Jim Host (born 1937), American businessman
* Michel Host ...
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
by intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
localization and adjustment of the cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
composition to mimic the host cell membrane.
Cytoadherence
Adherence of ''M. pneumoniae'' to a host cell (usually a respiratory tract
The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa.
Air is breathed in through the nose to th ...
cell, but occasionally an erythrocyte
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
or urogenital lining cell) is the initiating event for pneumonic disease and related symptoms.[ The specialized attachment ]organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
is a polar
Polar may refer to:
Geography
Polar may refer to:
* Geographical pole, either of two fixed points on the surface of a rotating body or planet, at 90 degrees from the equator, based on the axis around which a body rotates
* Polar climate, the c ...
, electron dense and elongated cell extension that facilitates motility
Motility is the ability of an organism to move independently, using metabolic energy.
Definitions
Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
and adherence to host cells. It is composed of a central filament surrounded by an intracytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
ic space, along with a number of adhesins Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor.
Adherence is an essent ...
and structural and accessory proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
localized at the tip of the organelle.
A variety of proteins are known to contribute to the formation and functionality of the attachment organelle, including the accessory proteins HMW1–HMW5, P30, P56, and P90 that confer structure and adhesin support, and P1, P30 and P116 which are involved directly in attachment. This network of proteins participates not only in the initiation of attachment organelle formation and adhesion but also in motility
Motility is the ability of an organism to move independently, using metabolic energy.
Definitions
Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
.
The P1 adhesin (trypsin-sensitive protein) is a 120 kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
protein highly clustered on the surface of the attachment organelle tip in virulent
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...
mycoplasmas. Both the presence of P1 and its concentration on the cell surface are required for the attachment of ''M. pneumoniae'' to the host cell. ''M. pneumoniae'' cells treated with monoclonal antibodies
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodies ca ...
specific to the immunogenic
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:
* Wanted immunogenicity typically relates to vaccines, where the injectio ...
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
of the P1 adhesin have been shown to be inhibited in their ability to attach to the host cell surface by approximately 75%, suggesting P1 is a major component in adherence. These antibodies also decreased the ability of the cell to glide
Glide may refer to:
* Gliding flight, to fly without thrust
Computing
*Glide API, a 3D graphics interface
*Glide OS, a web desktop
*Glide (software), an instant video messenger
*Glide, a molecular docking software by Schrödinger (company), Schr� ...
quickly, which may contribute to decreased adherence to the host by hindering their capacity to locate a host cell. Furthermore, mutations in P1 or degradation by trypsin
Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting these long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the dig ...
treatment yield avirulent ''M. pneumoniae'' cells.[ Loss of proteins in the ]cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
involved in the localization of P1 in the tip structure, such as HMW1–HMW3, also cause avirulence
The gene-for-gene relationship was discovered by Harold Henry Flor who was working with rust (''Melampsora lini'') of flax (''Linum usitatissimum''). Flor showed that the inheritance of both resistance in the host and parasite ability to cause di ...
due to the lack of adhesin clustering.[ Another protein considered to play an important role in adherence is P30, as ''M. pneumoniae'' cells with mutations in this protein or that have had ]antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
raised against P30 are incapable of adhering to host cells. P30 is not involved in the localization of P1 in the tip structure since P1 is trafficked to the attachment organelle in P30 mutants, but rather it may function as a receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
-binding accessory adhesin.[ P30 mutants also display distinct morphological features such as multiple lobes and a rounded shape as opposed to elongated, which suggests P30 may interact with the cytoskeleton during formation of the attachment organelle.]
A number of eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cell surface components have been implicated in the adherence of ''M. pneumoniae'' cells to the respiratory tract epithelium
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
. Among them are sialoglycoconjugates, sulfated glycolipids
Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connec ...
, glycoproteins
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
, fibronectin
Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...
, and neuraminic acid
Neuraminic acid (5-amino-3,5-dideoxy-D-''glycero''-D-''galacto''-non-2-ulosonic acid) is an acidic (in particular ulosonic) amino sugar with a backbone formed by nine carbon atoms. Although 9-carbon sugars do not occur naturally, neuraminic ...
receptors. Lectins
Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in rec ...
on the surface of the bacterial cells are capable of binding oligosaccharide
An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sugar ...
chains on glycolipids and glycoproteins to facilitate attachment, in addition to the proteins TU and pyruvate dehydrogenase E1 β, which bind to fibronectin.
Intracellular localization
''Mycoplasma pneumoniae'' is known to evade host immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
detection, resist antibiotic treatment, and cross mucosal
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
barriers, which may be due to its ability to fuse with host cells and survive intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
ly. In addition to the close physical proximity of ''M. pneumoniae'' and host cells, the lack of cell wall
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...
and peculiar cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
components, like cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
, may facilitate fusion (1). Internal localization may produce chronic or latent infections as ''M. pneumoniae'' is capable of persisting, synthesizing DNA, and replicating within the host cell even after treatment with antibiotics. The exact mechanism of intracellular localization is unknown, however the potential for cytoplasmic sequestration within the host explains the difficulty in completely eliminating ''M. pneumoniae'' infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s in afflicted individuals.[
]
Immune response
In addition to evasion of host immune system by intracellular localization, ''M. pneumoniae'' can change the composition of its cell membrane to mimic the host cell membrane and avoid detection by immune system cells. ''M. pneumoniae'' cells possess a number of protein and glycolipid antigens
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
that elicit immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
s, but variation of these surface antigens would allow the infection to persist long enough for ''M. pneumoniae'' cells to fuse with host cells and escape detection. The similarity between the compositions of ''M. pneumoniae'' and human cell membranes can also result in autoimmune response
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
s in several organs and tissues.[
]
Cytotoxicity and organismal effects
The main cytotoxic
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'').
Cell physiology
Treating cells ...
effect of ''M. pneumoniae'' is local disruption of tissue and cell structure along the respiratory tract epithelium due to its close proximity to host cells. Attachment of the bacteria to host cells can result in loss of cilia
The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
, a reduction in metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
, biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
, and import of macromolecules
A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
, and, eventually, infected cells may be shed from the epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
lining.[ M. pneumoniae produces a unique virulence factor known as Community Acquired Respiratory Distress Syndrome (CARDS) toxin. The CARDS toxin most likely aids in the colonization and pathogenic pathways of M. pneumoniae, leading to inflammation and airway dysfunction. In addition, the formation of ]hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%� ...
is a key virulence factor
Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following ...
in ''M. pneumoniae'' infections.[ Attachment of ''M. pneumoniae'' to ]erythrocytes
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
permits diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
of hydrogen peroxide from the bacteria to the host cell without detoxification
Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of ...
by catalase
Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...
or peroxidase
Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides.
Functionality
Peroxidases typically ca ...
, which can injure the host cell by reducing glutathione
Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...
, damaging lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
membranes and causing protein denaturation
In biochemistry, denaturation is a process in which proteins or nucleic acids lose the quaternary structure, tertiary structure, and secondary structure which is present in their native state, by application of some external stress or compound ...
. Local damage may also be a result of lactoferrin
Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, s ...
acquisition and subsequent hydroxyl radical
The hydroxyl radical is the diatomic molecule . The hydroxyl radical is very stable as a dilute gas, but it decays very rapidly in the condensed phase. It is pervasive in some situations. Most notably the hydroxyl radicals are produced from the ...
, superoxide anion and peroxide
In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable.
The most common peroxide is hydrogen p ...
formation.[ The cytotoxic effects of ''M. pneumoniae'' infections translate into common symptoms like ]coughing
A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three phas ...
and lung irritation
Irritation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant. Irritants are typically thought of as chemical age ...
that may persist for months after infection has subsided. Local inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
and hyperresponsiveness by infection induced cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
production has been associated with chronic conditions such as bronchial asthma and has also been linked to progression of symptoms in individuals with cystic fibrosis
Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...
and COPD
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce mu ...
.[
]
Epidemiology
The incidence of disease does not appear to be related to season or geography; however, infection tends to occur more frequently during the summer and fall months when other respiratory pathogens
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
are less prevalent. Reinfection and epidemic
An epidemic (from Ancient Greek, Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of patients among a given population within an area in a short period of time.
Epidemics ...
cycling is thought to be a result of P1 adhesin subtype variation.[ Approximately 40% of community-acquired ]pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
is due to ''M. pneumoniae'' infections, with children and elderly individuals being most susceptible
Susceptibility may refer to:
Physics and engineering
In physics the susceptibility is a quantification for the change of an extensive property under variation of an intensive property. The word may refer to:
* In physics, the susceptibility of a ...
, however no personal risk factors for acquiring ''M. pneumoniae'' induced pneumonia have been determined. Transmission
Transmission may refer to:
Medicine, science and technology
* Power transmission
** Electric power transmission
** Propulsion transmission, technology allowing controlled application of power
*** Automatic transmission
*** Manual transmission
*** ...
of ''M. pneumoniae'' can only occur through close contact and exchange of aerosols
An aerosol is a suspension of fine solid particles or liquid droplets in air or another gas. Aerosols can be natural or anthropogenic. Examples of natural aerosols are fog or mist, dust, forest exudates, and geyser steam. Examples of anthrop ...
by coughing due to the increased susceptibility of the cell wall
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...
-lacking organism to desiccation
Desiccation () is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic (attracts and holds water) substance that induces or sustains such a state in its local vicinity in a moderately sealed container.
...
. Outbreak
In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
s of ''M. pneumoniae'' infections tend to occur within groups of people in close and prolonged proximity, including schools, institutions, military bases, and households.[
]
Symptoms of infection
''M. pneumoniae'' is known to cause a host of symptoms such as primary atypical pneumonia, tracheobronchitis Tracheobronchitis is inflammation of the trachea and bronchi. It is characterised by a cough, fever, and purulent (containing pus) sputum and is therefore suggestive of pneumonia. It is classified as a respiratory tract infection.
Tracheobronchitis ...
, and upper respiratory tract disease. Primary atypical pneumonia is one of the most severe types of manifestation, with tracheobronchitis being the most common symptom and another 15% of cases, usually adults, remain asymptomatic. Symptomatic infections tend to develop over a period of several days and manifestation of pneumonia can be confused with a number of other bacterial pathogens and conditions that cause pneumonia. Tracheobronchitis is most common in children due to a reduced immune system capacity, and up to 18% of infected children require hospitalization
A hospital is a health care institution providing patient treatment with specialized Medical Science, health science and auxiliary healthcare staff and medical equipment. The best-known type of hospital is the general hospital, which typically ...
.[ Common mild symptoms include ]sore throat
Sore throat, also known as throat pain, is pain or irritation of the throat. Usually, causes of sore throat include
* viral infections
* group A streptococcal infection (GAS) bacterial infection
* pharyngitis (inflammation of the throat)
* tonsi ...
, wheezing
A wheeze is a continuous, coarse, whistling sound produced in the respiratory airways during breathing. For wheezes to occur, some part of the respiratory tree must be narrowed or obstructed (for example narrowing of the lower respiratory tract ...
and coughing
A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three phas ...
, fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
, headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
, rhinitis
Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip.
The inflammation is caused by viruses, bacteria, irritants o ...
, myalgia
Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...
and feelings of unease, in which symptom intensity and duration can be limited by early treatment with antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
. Rarely, ''M. pneumoniae'' pneumonia results in death due to lesions
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals.
Types
There is no designated classifi ...
and ulceration
An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
of the epithelial lining, pulmonary edema
Pulmonary edema, also known as pulmonary congestion, is excessive edema, liquid accumulation in the parenchyma, tissue and pulmonary alveolus, air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia an ...
, and bronchiolitis obliterans
Bronchiolitis obliterans (BO), also known as obliterative bronchiolitis, constrictive bronchiolitis and popcorn lung, is a disease that results in obstruction of the smallest airways of the lungs (bronchioles) due to inflammation. Symptoms include ...
. Extrapulmonary symptoms such as autoimmune responses, central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
complications, and dermatological
Dermatology is the branch of medicine dealing with the skin.''Random House Webster's Unabridged Dictionary.'' Random House, Inc. 2001. Page 537. . It is a speciality with both medical and surgical aspects. A dermatologist is a specialist medical ...
disorders have been associated with ''M. pneumoniae'' infections in up to 25% of cases.[
]
Diagnosis
Diagnosis
Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
of ''Mycoplasma pneumoniae'' infections is complicated by the delayed onset of symptoms
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an disease, illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormali ...
and the similarity of symptoms to other pulmonary conditions. Often, ''M. pneumoniae'' infections are diagnosed as other conditions and, occasionally, non-pathogenic
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
mycoplasmas present in the respiratory tract are mistaken for ''M. pneumoniae''.[ Historically, diagnosis of ''M. pneumoniae'' infections was made based on the presence of cold ]agglutinins
Agglutination is the clumping of particles. The word ''agglutination'' comes from the Latin '' agglutinare'' (glueing to).
Agglutination is the process that occurs if an antigen is mixed with its corresponding antibody called isoagglutinin. Th ...
and the ability of the infected material to reduce tetrazolium. Causative diagnosis is dependent upon laboratory
A laboratory (; ; colloquially lab) is a facility that provides controlled conditions in which scientific or technological research, experiments, and measurement may be performed. Laboratory services are provided in a variety of settings: physicia ...
testing, however these methods are more practical in epidemiological
Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population.
It is a cornerstone of public health, and shapes policy decisions and evidenc ...
studies than in patient diagnosis.[ ]Culture
Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups.Tyl ...
tests are rarely used as diagnostic tools; rather immunoblotting
The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...
, immunofluorescent staining, hemadsorption tests, tetrazolium reduction, metabolic
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
inhibition tests, serological
Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
assays, and polymerase chain reaction
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(PCR) are used for diagnosis and characterization of bacterial pneumonic infections.[ PCR is the most rapid and effective way to determine the presence of ''M. pneumoniae'', however the procedure does not indicate the activity or viability of the cells present.] Enzyme immunoassay An enzyme immunoassay is any of several immunoassay methods that use an enzyme bound to an antigen or antibody. These may include:
* Enzyme-linked immunosorbent assay (ELISA)
* Enzyme multiplied immunoassay technique (EMIT)
* Fluorescent enzyme ...
(EIA) serological assays are the most common method of ''M. pneumoniae'' detection used in patient diagnosis due to the low cost and relatively short testing time. One drawback of serology is that viable organisms are required, which may overstate the severity of infection.[ Neither of these methods, along with others, has been available to medical professionals in a rapid, efficient and inexpensive enough form to be used in routine diagnosis, leading to decreased ability of physicians to diagnose ''M. pneumoniae'' infections.
]
Treatment and prevention
The majority of antibiotics used to treat ''M. pneumoniae'' infections are targeted at bacterial rRNA
Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosoma ...
in ribosomal
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to fo ...
complexes, including macrolides
The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macro ...
, tetracycline
Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including Acne vulgaris, acne, cholera, brucellosis, plague (disease), plague, malaria, and sy ...
, ketolides, and fluoroquinolone
A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as wel ...
, many of which can be administered orally. Macrolides are capable of reducing hyperresponsiveness and protecting the epithelial lining from oxidative
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
and structural damage, however they are capable only of inhibiting bacteria (bacteriostatic
A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfect ...
) and are not able to cause bacterial cell death. The most common macrolides used in the treatment of infected children in Japan are erythromycin
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...
and clarithromycin
Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, ''H. pylori'' infection, and Lyme disease, among others. Clarith ...
, which inhibit bacterial protein synthesis by binding 23S rRNA 3S may refer to:
* 3S, for single, seventies/1970s, stuck, a slang form of sheng nu, a derogatory Chinese term referring to unmarried women in their mid to late twenties
* 3S gondola lift
* 3-S treatment, a method for dealing with unwanted or unwelc ...
. Administration of antibiotics has been proven to reduce the longevity and intensity of ''M. pneumoniae'' infections in comparison to cases left untreated. Additionally, some high-dose steroid therapies have shown to reverse neurological
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
effects in children with complicated infections.[
The difficulty in eradicating ''Mycoplasma pneumoniae'' infections is due to the ability of the bacterium to persist within an individual, as well as the lack of cell wall in ''M. pneumoniae'', which renders multiple antibiotics directed at the bacterial cell wall ineffective in treating infections.][ ''M. pneumoniae'' therefore displays resistance to antimicrobials such as ]β-lactams
A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...
, glycopeptides, sulfonamides
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
, trimethoprim
Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for ''Pneumocystis'' pneumonia in peop ...
, polymixins, nalidixic acid
Nalidixic acid (tradenames Nevigramon, NegGram, Wintomylon and WIN 18,320) is the first of the synthetic quinolone antibiotics.
In a technical sense, it is a naphthyridone, not a quinolone: its ring structure is a 1,8-naphthyridine nucleus that ...
, and rifampin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used tog ...
. Antimicrobial drug resistance rates for ''Mycoplasma pneumoniae'' were determined in clinical specimens and isolates obtained during 2011–2012 in Ontario, Canada. Of 91 ''M. pneumoniae'' drug-resistant specimens, 11 (12.1%) carried nucleotide mutations associated with macrolide
The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrol ...
resistance in the 23S rRNA 3S may refer to:
* 3S, for single, seventies/1970s, stuck, a slang form of sheng nu, a derogatory Chinese term referring to unmarried women in their mid to late twenties
* 3S gondola lift
* 3-S treatment, a method for dealing with unwanted or unwelc ...
gene. None of the ''M. pneumoniae'' specimens were resistant to fluoroquinolone
A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as wel ...
s or tetracycline
Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including Acne vulgaris, acne, cholera, brucellosis, plague (disease), plague, malaria, and sy ...
s.
Doxycycline can be used for treating ''Mycoplasma pneumonia'', which usually presents with persistent, incessant cough that lasts for several weeks and shows interstitial pulmonary infiltrates on a chest x-ray.
Vaccine
A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
design for ''M. pneumoniae'' has been focused primarily on prevention of host cell attachment, which would prevent initiation of cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'').
Cell physiology
Treating cells ...
and subsequent symptoms.[ To date, vaccines targeted at the P1 adhesin have shown no reduction in the onset of infection, and some vaccine trials resulted in worsened symptoms due to immune system ]sensitization
Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole class of stim ...
.[ Recent experiments in mouse models have linked this phenomenon to immune system sensitization by the lipid moieties of ''M. pneumoniae'' lipoproteins.] Introduction of peptides
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
that block adhesion receptors on the surface of the host cell may also be able to prevent attachment of ''M. pneumoniae''.
Transmission of ''Mycoplasma pneumoniae'' infections is difficult to limit because of the several day period of infection before symptoms appear. The lack of proper diagnostic tools and effective treatment for the bacterium also contribute to the outbreak of infection. Using network theory
Network theory is the study of graphs as a representation of either symmetric relations or asymmetric relations between discrete objects. In computer science and network science, network theory is a part of graph theory: a network can be defi ...
, Meyers ''et al.'' analyzed the transmission of ''M. pneumoniae'' infections and developed control strategies based on the created model. They determined that cohorting patients is less effective due to the long incubation period
Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the i ...
, and so the best method of prevention is to limit caregiver
A caregiver or carer is a paid or unpaid member of a person's social network who helps them with activities of daily living. Since they have no specific professional training, they are often described as informal caregivers. Caregivers most commo ...
-patient interactions and reduce the movement of caregivers to multiple wards
Ward may refer to:
Division or unit
* Hospital ward, a hospital division, floor, or room set aside for a particular class or group of patients, for example the psychiatric ward
* Prison ward, a division of a penal institution such as a priso ...
.
See also
* Mycoplasma
''Mycoplasma'' is a genus of bacteria that, like the other members of the class ''Mollicutes'', lack a cell wall around their cell membranes. Peptidoglycan (murein) is absent. This characteristic makes them naturally resistant to antibiotics ...
* Mollicutes
Mollicutes is a class of bacteria distinguished by the absence of a cell wall. The word "Mollicutes" is derived from the Latin ''mollis'' (meaning "soft" or "pliable"), and ''cutis'' (meaning "skin"). Individuals are very small, typically only 0. ...
* Bacterial pneumonia
Bacterial pneumonia is a type of pneumonia caused by bacterial infection.
Types
Gram-positive
''Streptococcus pneumoniae'' () is the most common bacterial cause of pneumonia in all age groups except newborn infants. ''Streptococcus pneumoniae'' ...
References
''This article incorporates public domain text from the CDC as cited.''
Further reading
*
*
*
*
*
*
*
* See also Hayflick's comments on Meredith Wadman's book, "The Vaccine Race: Science, Politics and the Human Costs of Defeating Disease", 201
''Errors in "The Vaccine Race" book''
External links
''Mycoplasma pneumoniae'' genome
Type strain of ''Mycoplasma pneumoniae'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q310904
Pathogenic bacteria
Bacteria described in 1963
pneumoniae