Pneumococcus
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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 ''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 occurs ...
. They are usually found in pairs ( diplococci) 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 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 pathogenic 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, snee ...
s and by auto inoculation in persons carrying the bacteria in their upper respiratory tracts. It can be a cause of neonatal infections. ''Streptococcus pneumoniae'' is the main cause of
community acquired pneumonia Community-acquired pneumonia (CAP) refers to pneumonia (any of several lung diseases) contracted by a person outside of the healthcare system. In contrast, hospital-acquired pneumonia (HAP) is seen in patients who have recently visited a hospital ...
and meningitis in children and the elderly, and of sepsis 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 immune ...
. The organism also causes many types of
pneumococcal infection A pneumococcal infection is an infection caused by the bacterium ''Streptococcus pneumoniae'', which is also called the pneumococcus. ''S. pneumoniae'' is a common member of the bacterial flora colonizing the nose and throat of 5–10% of healthy ...
s 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 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, otitis media, conjunctivitis, meningitis, 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 Acute septic arthritis, infectious arthritis, suppurative arthritis, osteomyelitis, or joint infection is the invasion of a joint by an infectious agent resulting in joint inflammation. Generally speaking, symptoms typically include redness, h ...
, endocarditis,
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,
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 The viridans streptococci are a large group of commensal streptococcal Gram-positive bacteria species that are α-hemolytic, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), although ...
, 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 by bile, 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 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 serotypes are known, and these types differ in virulence,
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.. 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 Frederick Griffith (1877–1941) was a British bacteriologist whose focus was the epidemiology and pathology of bacterial pneumonia. In January 1928 he reported what is now known as Griffith's Experiment, the first widely accepted demonstrati ...
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 demonstrated that the transforming factor in
Griffith's experiment Griffith's experiment, reported in 1928 by Frederick Griffith, was the first experiment suggesting that bacteria are capable of transferring genetic information through a process known as transformation. Griffith's findings were followed by res ...
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 of ''S. pneumoniae'' is a closed, circular DNA structure that contains between 2.0 and 2.1 million base pairs depending on the
strain Strain may refer to: Science and technology * Strain (biology), variants of plants, viruses or bacteria; or an inbred animal used for experimental purposes * Strain (chemistry), a chemical stress of a molecule * Strain (injury), an injury to a mu ...
. 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. 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 Lantibiotics are a class of polycyclic peptide antibiotics that contain the characteristic thioether amino acids lanthionine or methyllanthionine, as well as the Saturated and unsaturated compounds, unsaturated amino acids dehydroalanine, and 2-Am ...
.


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 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 are ...
, it must enter a special physiological state called competence. Competence in ''S. pneumoniae'' is induced by DNA-damaging agents such as
mitomycin C Mitomycin C is a mitomycin that is used as a chemotherapeutic agent by virtue of its antitumour activity. Medical uses It is given intravenously to treat upper gastro-intestinal cancers (e.g. esophageal carcinoma), anal cancers, and breast ...
,
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 ...
antibiotics (
norfloxacin Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, g ...
,
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), and
topoisomerase inhibitor Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). Topoisomerase plays important roles in cellular rep ...
s. 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 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 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 t ...
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, an anti
phagocytic Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is c ...
capsule, various adhesins, and
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 ...
cell wall components are all major virulence factors. After ''S. pneumoniae'' colonizes the air sacs 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 side ...
, 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 Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...
. Sepsis is caused by overwhelming response to an infection and leads to tissue damage,
organ failure Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention. It is not a diagnosis ...
, 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 vaccines have been developed to protect against invasive infection. The World Health Organization 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 Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any ...
enzyme or using the SnoopTag/SnoopCatcher reaction. Various
glycoside hydrolases Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalyze the hydrolysis of glycosidic bonds in complex sugars. They are extremely common enzymes with roles in nature including degradation of biomass such as cellulose (cel ...
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 ...
'' 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 substrates, and the enzyme converts the substrates into different molecules known as products ...
enoyl-acyl carrier protein reductase, (essential for the biosynthesis of fatty acids) 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


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