Streptococcus pneumoniae
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''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the
genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial n ...
Streptococcus. They are usually found in pairs ( diplococci) and do not form spores and are non motile. As a significant human pathogenic bacterium ''S. pneumoniae'' was recognized as a major cause of
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 severi ...
in the late 19th century, and is the subject of many humoral immunity studies. ''Streptococcus pneumoniae'' resides asymptomatically in healthy carriers typically colonizing the respiratory tract, sinuses, and nasal cavity. However, in susceptible individuals with weaker immune systems, such as the elderly and young children, the bacterium may become
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 ger ...
ic and spread to other locations to cause disease. It spreads by direct person-to-person contact via
respiratory droplet A respiratory droplet is a small aqueous droplet produced by exhalation, consisting of saliva or mucus and other matter derived from respiratory tract surfaces. Respiratory droplets are produced naturally as a result of breathing, speaking, sn ...
s and by auto inoculation in persons carrying the bacteria in their upper respiratory tracts. It can be a cause of
neonatal infection Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or in the first four weeks of life (neonatal period). Neonatal infections may be contracted by mother to child transmission, in the birth canal dur ...
s. ''Streptococcus pneumoniae'' is the main cause of community acquired pneumonia and meningitis in children and the elderly, and of
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is foll ...
in those infected with
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
. The organism also causes many types of pneumococcal infections other than
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 severi ...
. These invasive pneumococcal diseases include bronchitis, rhinitis,
acute sinusitis Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, headac ...
, otitis media,
conjunctivitis Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The ...
, meningitis, sepsis, osteomyelitis, septic arthritis,
endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
, peritonitis, pericarditis, cellulitis, and brain abscess. ''Streptococcus pneumoniae'' can be differentiated from the viridans streptococci, some of which are also alpha-hemolytic, using an optochin test, as ''S. pneumoniae'' is optochin-sensitive. ''S. pneumoniae'' can also be distinguished based on its sensitivity to
lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
by bile, the so-called "bile solubility test". The encapsulated, Gram-positive,
coccoid Coccoid means shaped like or resembling a coccus, that is, spherical.The noun coccoid or coccoids may refer to: * a level of organization, characterized by unicellular, non-flagellated, non-amoeboid organisms, with a definite shape, in general b ...
bacteria have a distinctive morphology on Gram stain, lancet-shaped diplococci. They have a polysaccharide capsule that acts as a virulence factor for the organism; more than 100 different serotypes are known, and these types differ in virulence, prevalence, and extent of drug resistance.


History

In 1881, the organism, known later in 1886 as the pneumococcus for its role as a cause of pneumonia, was first isolated simultaneously and independently by the U.S. Army
physician A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...
George Sternberg. and the French chemist Louis Pasteur.. The organism was termed ''Diplococcus pneumoniae'' from 1920 because of its characteristic appearance in Gram-stained sputum. It was renamed ''Streptococcus pneumoniae'' in 1974 because it was very similar to streptococci. ''Streptococcus pneumoniae'' played a central role in demonstrating that genetic material consists of DNA. In 1928, Frederick Griffith demonstrated transformation of life turning harmless pneumococcus into a lethal form by co-inoculating the live pneumococci into a mouse along with heat-killed virulent pneumococci. In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty demonstrated that the transforming factor in Griffith's experiment was not
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, respon ...
, as was widely believed at the time, but DNA. Avery's work marked the birth of the molecular era of genetics.


Genetics

The
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 ...
of ''S. pneumoniae'' is a closed, circular DNA structure that contains between 2.0 and 2.1 million base pairs depending on the strain. It has a core set of 1553
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 b ...
s, plus 154 genes in its virulome, which contribute to virulence and 176 genes that maintain a noninvasive
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...
. Genetic information can vary up to 10% between strains. The pneumococcal genome is known to contain a large and diverse repertoire of antimicrobial peptides, including 11 different lantibiotics.


Transformation

Natural bacterial transformation involves the transfer of DNA from one bacterium to another through the surrounding medium. Transformation is a complex developmental process requiring
energy In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of hea ...
and is dependent on expression of numerous genes. In S. pneumoniae, at least 23 genes are required for transformation. For a bacterium to bind, take up, and recombine exogenous DNA into its
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 ...
, it must enter a special physiological state called
competence Competence may refer to: *Competence (geology), the resistance of a rock against deformation or plastic flow. *Competence (human resources), a standardized requirement for an individual to properly perform a specific job *Competence (law), the me ...
. Competence in ''S. pneumoniae'' is induced by DNA-damaging agents such as mitomycin C,
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 ...
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
s ( norfloxacin, levofloxacin and moxifloxacin), and topoisomerase inhibitors. Transformation protects ''S. pneumoniae'' against the bactericidal effect of mitomycin C. Michod et al. summarized evidence that induction of competence in ''S. pneumoniae'' is associated with increased resistance to oxidative stress and increased expression of the RecA protein, a key component of the recombinational repair machinery for removing DNA damages. On the basis of these findings, they suggested that transformation is an adaptation for repairing oxidative DNA damages. ''S. pneumoniae'' infection stimulates polymorphonuclear leukocytes (granulocytes) to produce an oxidative burst that is potentially lethal to the bacteria. The ability of ''S. pneumoniae'' to repair the oxidative DNA damages in its genome, caused by this host defense, likely contributes to this pathogen's virulence. Consistent with this premise, Li et al. reported that, among different highly transformable ''S. pneumoniae'' isolates, nasal colonization fitness and virulence (lung infectivity) depend on an intact competence system.


Infection

''Streptococcus pneumoniae'' is part of the normal upper respiratory tract
flora Flora (: floras or florae) is all the plant life present in a particular region or time, generally the naturally occurring (indigenous (ecology), indigenous) native plant, native plants. The corresponding term for animals is ''fauna'', and for f ...
. As with many natural flora, it can become pathogenic under the right conditions, typically when the immune system of the host is suppressed. Invasins, such as pneumolysin, an anti phagocytic capsule, various
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 esse ...
, and immunogenic cell wall components are all major virulence factors. After ''S. pneumoniae'' colonizes the air sacs of the lungs, the body responds by stimulating the inflammatory response, causing plasma, blood, and white blood cells to fill the alveoli. This condition is called pneumonia.


Diseases and symptoms

Pneumonia is the most common of the ''S. pneumoniae'' diseases which include symptoms such as fever and chills, cough, rapid breathing, difficulty breathing, and chest pain. For the elderly, they may include confusion, low alertness, and the former listed symptoms to a lesser degree. Pneumococcal meningitis is an infection of the tissue covering the brain and spinal cord. Symptoms include stiff neck, fever, headache, confusion, and photophobia. Sepsis is caused by overwhelming response to an infection and leads to tissue damage, organ failure, and even death. The symptoms include confusion, shortness of breath, elevated heart rate, pain or discomfort, over-perspiration, fever, shivering, or feeling cold.


Vaccine

Due to the importance of disease caused by ''S. pneumoniae'', several
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. ...
s have been developed to protect against invasive infection. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
recommends routine childhood pneumococcal vaccination; it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom, the United States, and South Africa.


Biotechnology

Components from ''S. pneumoniae'' have been harnessed for a range of applications in biotechnology. Through engineering of surface molecules from this bacterium, proteins can be irreversibly linked using the sortase enzyme or using the SnoopTag/SnoopCatcher reaction. Various glycoside hydrolases have also been cloned from ''S. pneumoniae'' to help analysis of cell glycosylation.


Interaction with ''Haemophilus influenzae''

Historically, '' Haemophilus influenzae'' has been a significant cause of infection, and both ''H. influenzae'' and ''S. pneumoniae'' can be found in the human upper respiratory system. A study of competition ''
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 and ...
'' revealed ''S. pneumoniae'' overpowered ''H. influenzae'' by attacking it with hydrogen peroxide. However, in a study adding both bacteria to the nasal cavity of a mouse within two weeks, only ''H. influenzae'' survives; further analysis showed that neutrophils exposed to dead ''H. influenzae'' were more aggressive in attacking ''S. pneumoniae''.Full text
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Diagnosis

Diagnosis is generally made based on clinical suspicion along with a positive culture from a sample from virtually any place in the body. ''S. pneumoniae'' is, in general, optochin sensitive, although optochin resistance has been observed. The recent advances in next-generation sequencing and comparative genomics have enabled the development of robust and reliable molecular methods for the detection and identification of ''S. pneumoniae''. For instance, the ''Xisco'' gene was recently described as a biomarker for PCR-based detection of ''S. pneumoniae'' and differentiation from closely related species. Atromentin and leucomelone possess antibacterial activity, inhibiting the
enzyme 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 ...
enoyl-acyl carrier protein reductase Enoyl-acyl carrier protein reductase (or ENR) (), is a key enzyme of the type II fatty acid synthesis (FAS) system. ENR is an attractive target for narrow-spectrum antibacterial drug discovery because of its essential role in metabolism and its seq ...
, (essential for the biosynthesis of
fatty acid 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, ...
s) in ''S. pneumoniae''.


Resistance

Resistant pneumococcal strains are called penicillin-resistant pneumococci (PRP), penicillin-resistant ''Streptococcus pneumoniae'' (PRSP), ''Streptococcus pneumoniae'' penicillin resistant (SPPR) or drug-resistant ''Strepotococcus pneumoniae'' (DRSP). In 2015, in the US, there were an estimated 30,000 cases, and in 30% of them the strains were resistant to one or more antibiotics.


See also

* Transformation (genetics) *
Pneumococcal Awareness Council of Experts The Pneumococcal Awareness Council of Experts (PACE) is a project of the Sabin Vaccine Institute and is composed of global experts in infectious diseases and vaccines. Established in December 2006, The Council seeks to raise awareness among policy ...


References


External links


GAVI Alliance

PneumoADIP

PATH's Vaccine Resource Library pneumococcal resources
*
Type strain of ''Streptococcus pneumoniae'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q221179 Bacteria described in 1884 Gram-positive bacteria Pathogenic bacteria Pneumonia Polysaccharide encapsulated bacteria Streptococcaceae