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''Mycoplasma'' is a genus of
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 am ...
that, like the other members of the class '' Mollicutes'', lack a
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 mec ...
around their
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 (t ...
s. Peptidoglycan ( murein) is absent. This characteristic makes them naturally resistant to antibiotics that target cell wall synthesis (like the beta-lactam antibiotics). They can be parasitic or
saprotrophic Saprotrophic nutrition or lysotrophic nutrition is a process of chemoheterotrophic extracellular digestion involved in the processing of decayed (dead or waste) organic matter. It occurs in saprotrophs, and is most often associated with fungi ...
. Several species are
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 g ...
ic in humans, including '' M. pneumoniae'', which is an important cause of "walking" pneumonia and other respiratory disorders, and ''
M. genitalium ''Mycoplasma genitalium'' (''MG'', commonly known as Mgen) is a sexually transmitted, small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in humans. Medical reports published in 2007 and 20 ...
'', which is believed to be involved in pelvic inflammatory diseases. ''Mycoplasma'' species (like the other species of the class ''Mollicutes'') are among the smallest organisms yet discovered, can survive without oxygen, and come in various shapes. For example, ''M. genitalium'' is flask-shaped (about 300 x 600 nm), while ''M. pneumoniae'' is more elongated (about 100 x 1000 nm), many ''Mycoplasma'' species are coccoid. Hundreds of ''Mycoplasma'' species infect animals. The trivial name “mycoplasma” (plural mycoplasmas or mycoplasms) is commonly used for all members of the class ''Mollicutes''. In scientific classification, the designation ''Mycoplasma'' refers exclusively to the genus, a member of the '' Mycoplasmataceae'', the only family of the order '' Mycoplasmatales'' (see “scientific classification”).


Etymology

The term "mycoplasma", from the Greek μύκης, ' (fungus) and πλάσμα, ' (formed), was first used by Albert Bernhard Frank in 1889 to describe an altered state of plant cell cytoplasm resulting from infiltration by fungus-like microorganisms. Julian Nowak later proposed the name mycoplasma for certain filamentous microorganisms imagined to have both cellular and acellular stages in their lifecycles, which could explain how they were visible with a microscope, but passed through filters impermeable to other bacteria. Later, the name for these mycoplasmas was pleuropneumonia-like organisms (PPLO), broadly referring to organisms similar in colonial morphology and filterability to the causative agent (a ''Mycoplasma'' species) of contagious bovine pleuropneumonia. At present, all these organisms are classified as ''Mollicutes'' and the term ''Mycoplasma'' refers solely to the genus.


Species that infect humans

Species of ''Mycoplasma'', other than those listed below, have been recovered from humans, but are assumed to have been contracted from a non-human host. The following species use humans as the primary host: * '' M. amphoriforme'' * '' M. buccale'' * '' M. faucium'' * '' M. fermentans'' * ''
M. genitalium ''Mycoplasma genitalium'' (''MG'', commonly known as Mgen) is a sexually transmitted, small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in humans. Medical reports published in 2007 and 20 ...
'' * '' M. hominis'' * '' M. incognitus'' * '' M. lipophilum'' * '' M. orale'' * '' M. penetrans'' * '' M. pirum'' * '' M. pneumoniae'' * '' M. primatum'' * '' M. salivarium'' * '' M. spermatophilum''


Pathophysiology

''Mycoplasma'' species have been isolated from women with
bacterial vaginosis Bacterial vaginosis (BV) is a disease of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urinati ...
. ''M. genitalium'' is found in women with
pelvic inflammatory disease Pelvic inflammatory disease, also known as pelvic inflammatory disorder (PID), is an infection of the upper part of the female reproductive system, namely the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be ...
. In addition, infection is associated with increased risk of cervicitis,
infertility Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal st ...
,
preterm birth Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is betwee ...
and
spontaneous abortion Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical ...
. ''Mycoplasma genitalium'' has developed resistance to some antibiotics. ''Mycoplasma'' species are associated with
infant respiratory distress syndrome Infantile respiratory distress syndrome (IRDS), also called respiratory distress syndrome of newborn, or increasingly surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants ...
,
bronchopulmonary dysplasia Bronchopulmonary dysplasia (BPD; part of the spectrum of chronic lung disease of infancy) is a chronic lung disease in which premature infants, usually those who were treated with supplemental oxygen, require long-term oxygen. The alveoli that are ...
, and intraventricular hemorrhage in preterm infants.


Characteristics

Over 100 species have been included in the genus ''Mycoplasma'', a member of the class '' Mollicutes.'' They are
parasite 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 h ...
s or commensals of humans, animals, and plants. The genus ''Mycoplasma'' uses
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...
and
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
hosts. Dietary nitrogen availability has been shown to alter codon bias and genome evolution in ''Mycoplasma'' and ''Phytoplasma''. ''Mycoplasma'' species are among the smallest free-living organisms (about 0.2 - 0.3 µm in diameter). They have been found in the pleural cavities of cattle suffering from pleuropneumonia. These organisms are often called MLO (mycoplasma-like organisms) or, formerly, PPLO (pleuropneumonia-like organisms).


Important characteristics of ''Mycoplasma'' species

# Cell wall is absent and plasma membrane forms the outer boundary of the cell. # Due to the absence of cell walls these organisms can change their shape and are pleomorphic. # Lack of nucleus and other membrane-bound organelles. # Genetic material is a single DNA duplex and is naked. # Ribosomes are 70S type. # Possess a replicating disc at one end which assists replication process and also the separation of the genetic materials. # Heterotrophic nutrition. Some live as saprophytes but the majority are parasites of plants and animals. The parasitic nature is due to the inability of mycoplasmal bacteria to synthesise the required growth factor.


Cell and colony morphology

Due to the lack of a rigid cell wall, ''Mycoplasma'' species (like all ''Mollicutes'') can contort into a broad range of shapes, from round to oblong. They are pleomorphic and therefore cannot be identified as rods, cocci or spirochetes. Colonies show the typical „fried egg” appearance (about 0.5 mm in diameter).


Reproduction

In 1954, using phase-contrast microscopy, continual observations of live cells have shown that ''Mycoplasma'' species ("mycoplasmas", formerly called pleuropneumonia-like organisms, PPLO, now classified as ''Mollicutes'') and L-form bacteria (previously also called L-phase bacteria) do not proliferate by binary fission, but by a uni- or multi-polar
budding Budding or blastogenesis is a type of asexual reproduction in which a new organism develops from an outgrowth or bud due to cell division at one particular site. For example, the small bulb-like projection coming out from the yeast cell is kno ...
mechanism. Microphotograph series of growing microcultures of different strains of PPLOs, L-form bacteria and, as a control, a Micrococcus species (dividing by binary fission) have been presented.  Additionally, electron microscopic studies have been performed.


Phylogeny

Previously, ''Mycoplasma'' species (often commonly called "mycoplasmas", now classified as '' Mollicutes'') were sometimes considered stable L-form bacteria or even viruses, but phylogenetic analysis has identified them as bacteria that have lost their cell walls in the course of evolution. The genus ''Mycoplasma'' as originally described is highly paraphyletic, as such it was redescibed by Gupta et al. 2018 and its emendation was accompanied by the removal of 78 species. The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN) and
National Center for Biotechnology Information The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. Th ...
(NCBI) Unassigned species: * "''Ca.'' M. aoti" Barker et al. 2011 * "''Ca.'' M. corallicola" Neulinger et al. 2009 * "''Ca.'' M. erythrocervae" Watanabe et al. 2010 * "''Ca.'' M. haematocervi" corrig. Watanabe et al. 2010 * "''Ca.'' M. haematodidelphidis" corrig. Messick et al. 2002 * "''Ca.'' M. haematomacacae" corrig. Maggi et al. 2013 * "''Ca.'' M. haematominiopteri" corrig. Millán et al. 2015 * "''Ca.'' M. haematonasua" Collere et al. 2021 * "''Ca.'' M. haematoparvum" Sykes et al. 2005 * "''Ca.'' M. haematovis" corrig. Hornok et al. 2009 * "''Ca.'' M. haemoalbiventris" Pontarolo et al. 2021 * "''Ca.'' M. haemobovis" Meli et al. 2010 * "''Ca.'' M. haemomeles" Harasawa, Orusa &Giangaspero 2014 * "''Ca.'' M. haemomuris" (Mayer 1921) Neimark et al. 2002 * "''Ca.'' M. haemoparvum" Kenny et al. 2004 * "''Ca.'' M. haemosphiggurus" Valente et al. 2021 * ''M. hafezii'' Ziegler et al. 2019 * "'' M. incognitus''" Lo et al. 1989 * "''M. insons''" May et al. 2007 * "''Ca.'' M. kahanei" Neimark et al. 2002 * ''M. miroungigenitalium'' Volokhov et al. 2022 * ''M. miroungirhinis'' Volokhov et al. 2022 * "''M. monodon''" Ghadersohi & Owens 1998 * ''M. phocoenae'' Volokhov et al. 2022 * ''M. phocoeninasale'' Volokhov et al. 2022 * "''M. pneumophila''" Lyerova et al. 2008 * "''Ca.'' M. ravipulmonis" Neimark, Mitchelmore & Leach 1998 * ''M. seminis'' Fischer et al. 2021 * "''M. sphenisci''" Frasca et al. 2005 * "''M. tauri''" Spergser et al. 2021 * "''M. timone''" Greub & Raoult 2001 * "''Ca.'' M. tructae" Sanchez et al. 2020 * "''Ca.'' M. turicense" corrig. Willi et al. 2006 * "''M. volis''" Dillehay et al. 1995 * "''M. vulturii''" Oaks et al. 2004


Laboratory contaminant

''Mycoplasma'' species are often found in research laboratories as contaminants in
cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This tec ...
. Mycoplasmal cell culture contamination occurs due to contamination from individuals or contaminated cell culture
medium Medium may refer to: Science and technology Aviation * Medium bomber, a class of war plane * Tecma Medium, a French hang glider design Communication * Media (communication), tools used to store and deliver information or data * Medium ...
ingredients. ''Mycoplasma'' cells are physically small – less than 1  µm, so are difficult to detect with a conventional
microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisi ...
. Mycoplasmae may induce cellular changes, including
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
aberrations, changes 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 ...
and cell growth. Severe ''Mycoplasma'' infections may destroy a cell line. Detection techniques include
DNA probe In molecular biology, a hybridization probe (HP) is a fragment of DNA or RNA of usually 15–10000 nucleotide long which can be radioactively or fluorescently labeled. HP can be used to detect the presence of nucleotide sequences in analyzed RNA ...
, enzyme immunoassays, PCR, plating on sensitive
agar Agar ( or ), or agar-agar, is a jelly-like substance consisting of polysaccharides obtained from the cell walls of some species of red algae, primarily from ogonori (''Gracilaria'') and "tengusa" (''Gelidiaceae''). As found in nature, agar i ...
and staining with a DNA stain including DAPI or Hoechst. An estimated 11 to 15% of U.S. laboratory cell cultures are contaminated with mycoplasma. A Corning study showed that half of U.S. scientists did not test for ''Mycoplasma'' contamination in their cell cultures. The study also stated that, in former Czechoslovakia, 100% of cell cultures that were not routinely tested were contaminated while only 2% of those routinely tested were contaminated (study p. 6). Since the U.S. contamination rate was based on a study of companies that routinely checked for ''Mycoplasma'', the actual contamination rate may be higher. European contamination rates are higher and that of other countries are higher still (up to 80% of Japanese cell cultures). About 1% of published Gene Expression Omnibus data may have been compromised.Link
into RNAnet showing contamination of GEO. Press plot and drag blue crosshairs to expose links to description of experiments on human RNA samples
Several antibiotic-containing formulations of antimycoplasmal reagents have been developed over the years.
by Roche, MRA by ICN
Plasmocin
by Invivogen and more recentl

by TOKU-E.


Synthetic mycoplasma genome

A chemically synthesized genome of a mycoplasmal cell based entirely on synthetic DNA which can self-replicate has been referred to as '' Mycoplasma laboratorium''.


Pathogenicity

The P1 antigen is the primary virulence factor of mycoplasma. P1 is a membrane associated protein that allows adhesion to
epithelial cells 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 intercellu ...
. The P1 receptor is also expressed on erythrocytes which can lead to autoantibody
agglutination In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative la ...
from mycobacteria infection. Several ''Mycoplasma'' species can cause disease, including ''M. pneumoniae'', which is an important cause of atypical pneumonia (formerly known as "walking pneumonia"), and ''M. genitalium'', which has been associated with pelvic inflammatory diseases. Mycoplasma infections in humans are associated with skin eruptions in 17% of cases.


Sexually transmitted infections

''Mycoplasma'' and ''Ureaplasma'' species are not part of the normal vaginal flora. Some ''Mycoplasma'' species are spread through sexual contact.


Infertility

Some ''Mycoplasma'' species have a negative effect on fertility. '' M. hominis'' causes '' male sterility/Genitals inflammation'' in humans.


Infant mortality

Low birth-weight, preterm infants are susceptible to ''Mycoplasma'' infections.


Links to cancer

Several species of ''Mycoplasma'' are frequently detected in different types of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
cells. These species are: * ''M. fermentans'' * ''M. genitalium'' * ''M. hyorhinis'' * ''M. penetrans'' * ''U. urealyticum'' The majority of these ''Mycoplasma'' species have shown a strong correlation to malignant transformation in mammalian cells ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
''.


''Mycoplasma'' infection and host cell transformation

The presence of ''Mycoplasma'' was first reported in samples of cancer tissue in the 1960s. Since then, several studies tried to find and prove the connection between ''Mycoplasma'' and cancer, as well as how the bacterium might be involved in the formation of cancer. Several studies have shown that cells that are chronically infected with the bacteria go through a multistep transformation. The changes caused by chronic mycoplasmal infections occur gradually and are both morphological and genetic. The first visual sign of infection is when the cells gradually shift from their normal form to sickle-shaped. They also become hyperchromatic due to an increase of DNA in the nucleus of the cells. In later stages, the cells lose the need for solid support to grow and proliferate, as well as the normal contact-dependent inhibition cells.


Possible intracellular mechanisms of mycoplasmal malignant transformation

Karyotypic changes related to mycoplasma infections Cells infected with ''Mycoplasma'' for an extended period of time show significant chromosomal abnormalities. These include the addition of chromosomes, the loss of entire chromosomes, partial loss of chromosomes, and
chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal transl ...
. All of these genetic abnormalities may contribute to the process of malignant transformation. Chromosomal translocation and extra chromosomes help create abnormally high activity of certain proto-oncogenes, which caused by these genetic abnormalities and include those encoding c-myc, HRAS, and vav. The activity of proto-oncogenes is not the only cellular function that is affected; tumour suppressor genes are affected by the chromosomal changes induced by mycoplasma, as well. Partial or complete loss of chromosomes causes the loss of important genes involved in the regulation of cell proliferation. Two genes whose activities are markedly decreased during chronic infections with mycoplasma are the Rb and the p53 tumour suppressor genes. Another possible mechanism of carcinogenesis is RAC1 activation by a small GTPase-like protein fragment of Mycoplasma. A major feature that differentiates mycoplasmas from other carcinogenic pathogens is that the mycoplasmas do not cause the cellular changes by insertion of their own genetic material into the host cell. The exact mechanism by which the bacterium causes the changes is not yet known. ; Partial reversibility of malignant transformations The malignant transformation induced by ''Mycoplasma'' species is also different from that caused by other pathogens in that the process is reversible. The state of reversal is, however, only possible up to a certain point during the infection. The window of time when reversibility is possible varies greatly; it depends primarily on the ''Mycoplasma'' involved. In the case of ''M. fermentans'', the transformation is reversible until around week 11 of infection and starts to become irreversible between weeks 11 and 18. If the bacteria are killed using
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 preventio ...
(i.e.
ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin i ...
or Clarithromycin) before the irreversible stage, the infected cells should return to normal.


Connections to cancer ''in vivo'' and future research

Epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. ''M. genitalium'' and ''M. hyorhinis'' induce malignant phenotype in benign human prostate cells (BPH-1) that were not tumorigenic after 19 weeks of exposure.


Types of cancer associated with ''Mycoplasma''

Colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowe ...
: In a study to understand the effects of ''Mycoplasma'' contamination on the quality of cultured human colon cancer cells, a positive correlation was found between the number of'' M. hyorhinis'' cells present in the sample and the percentage of CD133-positive cells (a glycoprotein with an unknown function).
Gastric cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lym ...
: Strong evidence indicates the infection of'' M. hyorhinis'' contributes to the development of cancer within the stomach and increases the likelihood of malignant cancer cell development.
Lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, mali ...
: Studies on lung cancer have supported the belief that more than a coincidental positive correlation exists between the appearance of'' Mycoplasma'' strains in patients and the infection with tumorigenesis. Prostate cancer: p37, a protein encoded for by ''M. hyorhinis'', has been found to promote the invasiveness of prostate cancer cells. The protein also causes the growth, morphology, and gene expression of the cells to change, causing them to become a more aggressive phenotype. Renal cancer: Patients with renal cell carcinoma (RCC) exhibited a significantly high amount of Mycoplasma sp. compared with the healthy control group. This suggests ''Mycoplasma'' may play a role in the development of RCC.


See also

*
International Organization for Mycoplasmology The International Organisation for Mycoplasmology (IOM) is a non-profit making organisation founded in 1976. It promotes the study of mycoplasmas (mollicutes), bacteria without a cell wall, and the diseases associated with them. Areas of research ...
(IOM) *
Sexually transmitted disease Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are spread by sexual activity, especially vaginal intercourse, anal sex, and or ...
* Vaginal flora * Vaginal infection * Vaginal disease * Vaginal health * Phytoplasma * List of bacterial orders * List of bacteria genera


References


External links


Ureaplasma Infection: eMedicine Infectious Diseases
{{Authority control Mycoplasmataceae Bacteria genera Rodent-carried diseases Sexually transmitted diseases and infections Infectious causes of cancer Infertility Bacterial vaginosis