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''Streptococcus pneumoniae'', or pneumococcus, is a
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 bact ...
, 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 nom ...
Streptococcus. They are usually found in pairs (
diplococci A diplococcus (plural diplococci) is a round bacterium (a coccus) that typically occurs in the form of two joined cells. Types Examples of gram-negative diplococci are '' Neisseria spp.'' and ''Moraxella catarrhalis ''Moraxella catarrhal ...
) and do not form
spores In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, ...
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 severit ...
in the late 19th century, and is the subject of many
humoral immunity Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it i ...
studies. ''Streptococcus pneumoniae'' resides asymptomatically in healthy carriers typically colonizing the respiratory tract, sinuses, and
nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nasal ...
. 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 g ...
ic and spread to other locations to cause disease. It spreads by direct person-to-person contact via respiratory droplets 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 duri ...
s. ''Streptococcus pneumoniae'' is the main cause of community acquired pneumonia and
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
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 follo ...
in those infected with HIV. 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 severit ...
. These invasive pneumococcal diseases include
bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...
,
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, irrita ...
,
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 Otitis media is a group of inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, ...
,
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. Th ...
,
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
, sepsis,
osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
, 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 Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part o ...
,
pericarditis Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when sit ...
,
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
, and
brain abscess Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of infected material, coming from local (ear infection, dental abscess, infection of paranasal sinuses, infection of the mastoid air cells of the temporal bone ...
. ''Streptococcus pneumoniae'' can be differentiated from the viridans streptococci, some of which are also
alpha-hemolytic Hemolysis (from Greek αιμόλυση, meaning 'blood breakdown') is the breakdown of red blood cells. The ability of bacterial colonies to induce hemolysis when grown on blood agar is used to classify certain microorganisms. This is particularly ...
, using an
optochin Optochin (or ethylhydrocupreine hydrochloride) is a derivative of quinine introduced in 1911 by Morgenroth and Levy with the intention to treat pneumococci infection. In very high dilutions, it inhibits the growth of representatives of all four gr ...
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 b ...
by
bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bi ...
, the so-called "bile solubility test". The encapsulated, Gram-positive, coccoid bacteria have a distinctive morphology on Gram stain, lancet-shaped diplococci. They have a
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with w ...
capsule that acts as a
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 ...
for the organism; more than 100 different
serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the ep ...
s are known, and these types differ in
virulence 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 ...
,
prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
, and extent of
drug resistance Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...
.


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 Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named afte ...
.. The organism was termed ''Diplococcus pneumoniae'' from 1920 because of its characteristic appearance in Gram-stained
sputum Sputum is mucus that is coughed up from the lower airways (the trachea and bronchi). In medicine, sputum samples are usually used for a naked eye examination, microbiological investigation of respiratory infections and cytological investigatio ...
. It was renamed ''Streptococcus pneumoniae'' in 1974 because it was very similar to
streptococci ''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occu ...
. ''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 Oswald Theodore Avery Jr. (October 21, 1877 – February 20, 1955) was a Canadian-American physician and medical researcher. The major part of his career was spent at the Rockefeller Hospital in New York City. Avery was one of the first molecula ...
, Colin MacLeod, and
Maclyn McCarty Maclyn McCarty (June 9, 1911 – January 2, 2005) was an American geneticist, a research scientist described in 2005 as "the last surviving member of a Manhattan scientific team that overturned medical dogma in the 1940's and became the first to ...
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, res ...
, 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 pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both D ...
s 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 (biology), morphology or physical form and structure, its Developmental biology, developmental proc ...
. 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 ...
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 Exogenous DNA is DNA originating outside the organism of concern or study. Exogenous DNA can be found naturally in the form of partially degraded fragments left over from dead cells. These DNA fragments may then become integrated into the chromos ...
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 in ''S. pneumoniae'' is induced by DNA-damaging agents such as mitomycin C, fluoroquinolone
antibiotic 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 ...
s ( norfloxacin,
levofloxacin Levofloxacin, sold under the brand name Levaquin among others, is an antibiotic medication. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori (in combination with other medications), ...
and
moxifloxacin Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop. Common side effects ...
), 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 Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
and increased expression of the RecA protein, a key component of the recombinational repair machinery for removing
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
s. 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 are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...
(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 is all the plant life present in a particular region or time, generally the naturally occurring ( indigenous) native plants. Sometimes bacteria and fungi are also referred to as flora, as in the terms '' gut flora'' or '' skin flora''. ...
. 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 Pneumolysin is a virulence factor of the Gram-positive bacteria ''Streptococcus pneumoniae''. It is a pore-forming toxin of 53 kDa composed of 471 amino acids. It has a range of biological activity, including the ability to lyse and interfere wi ...
, 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 essent ...
, and immunogenic cell wall components are all major virulence factors. After ''S. pneumoniae'' colonizes the
air sacs Air sacs are spaces within an organism where there is the constant presence of air. Among modern animals, birds possess the most air sacs (9–11), with their extinct dinosaurian relatives showing a great increase in the pneumatization (presence o ...
of the
lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either si ...
, 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 Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...
.


Interaction with ''Haemophilus influenzae''

Historically, ''
Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bact ...
'' 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 a ...
'' revealed ''S. pneumoniae'' overpowered ''H. influenzae'' by attacking it with
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 ...
. However, in a study adding both bacteria to the
nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nasal ...
of a
mouse A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
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
/ref>


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 ...
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 Optochin (or ethylhydrocupreine hydrochloride) is a derivative of quinine introduced in 1911 by Morgenroth and Levy with the intention to treat pneumococci infection. In very high dilutions, it inhibits the growth of representatives of all four gr ...
sensitive, although optochin resistance has been observed. The recent advances in next-generation sequencing and
comparative genomics Comparative genomics is a field of biological research in which the genomic features of different organisms are compared. The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural ...
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 Atromentin is a natural chemical compound found in Agaricomycetes fungi in the orders Agaricales and Thelephorales. It can also be prepared by laboratory synthesis. Chemically, it is a polyphenol and a benzoquinone. Occurrences Atromentin has ...
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 substrates, and the enzyme converts the substrates into different molecules known as products ...
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 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 macromolecul ...
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, f ...
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) In molecular biology and genetics, transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane(s). For transformation to t ...
* Pneumococcal Awareness Council of Experts


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