''Streptococcus pyogenes'' is a
species
In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
of
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 ...
, aerotolerant
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
in the genus ''
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 ...
''. These bacteria are
extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
, and made up of non-motile and non-sporing
cocci
A coccus (plural cocci) is any bacterium or archaeon that has a spherical, ovoid, or generally round shape. Bacteria are categorized based on their shapes into three classes: cocci (spherical-shaped), bacillus (rod-shaped) and spiral ( of whi ...
(round cells) that tend to link in chains. They are clinically important for humans, as they are an infrequent, but usually
pathogenic, part of the
skin microbiota that can cause
Group A streptococcal infection
Group A streptococcal infections are a number of infections with ''Streptococcus pyogenes'' a group A streptococcus (GAS). ''S. pyogenes'' is a species of beta-hemolytic gram-positive bacteria that is responsible for a wide range of infections t ...
. ''S. pyogenes'' is the predominant species harboring the
Lancefield group A
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
, and is often called group A ''Streptococcus'' (GAS). However, both ''
Streptococcus dysgalactiae'' and the ''
Streptococcus anginosus'' group can possess group A antigen as well. Group A streptococci, when grown on
blood agar, typically produce small (2–3 mm) zones of
beta-hemolysis
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 particular ...
, a complete
destruction
Destruction may refer to:
Concepts
* Destruktion, a term from the philosophy of Martin Heidegger
* Destructive narcissism, a pathological form of narcissism
* Self-destructive behaviour, a widely used phrase that ''conceptualises'' certain kin ...
of
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s. The name group A (beta-hemolytic) ''Streptococcus'' (GABHS) is thus also used.
The species name is derived from Greek words meaning 'a chain' () of berries (
atinized from and
pus
Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during bacterial or fungal infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection ...
()-forming (''genes''), since a number of infections caused by the bacterium produce pus. The main criterion for differentiation between ''
Staphylococcus'' spp. and ''Streptococcus'' spp. is the
catalase test
Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...
. Staphylococci are catalase positive whereas streptococci are catalase-negative.
''S. pyogenes'' can be
cultured on fresh blood agar plates. Under ideal conditions, it has an
incubation period
Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the in ...
of 1 to 3 days.
An estimated 700 million GAS infections occur worldwide each year. While the overall mortality rate for these infections is less than 0.1%, over 650,000 of the cases are severe and invasive, with these cases having a mortality rate of 25%. Early recognition and treatment are critical;
diagnostic failure can result in
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 ...
and death.
Epidemiology
''S. pyogenes'' typically colonizes the throat, genital mucosa,
rectum, and skin. Of healthy individuals, 1% to 5% have throat, vaginal, or rectal carriage. In healthy children, such carriage rate varies from 2 to 17%. There are four methods for the transmission of this bacterium: inhalation of respiratory droplets, skin contact, contact with objects, surface, or dust that is contaminated with bacteria or, less commonly, transmission through food. Such bacteria can cause a variety of diseases such as
streptococcal pharyngitis,
rheumatic fever,
rheumatic heart disease
Rheumatic fever (RF) is an inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a streptococcal throat infection. Signs and symptoms include fever, multiple painful jo ...
, and
scarlet fever
Scarlet fever, also known as Scarlatina, is an infectious disease caused by ''Streptococcus pyogenes'' a Group A streptococcus (GAS). The infection is a type of Group A streptococcal infection (Group A strep). It most commonly affects childr ...
. Although pharyngitis is mostly viral in origin, about 15 to 30% of all pharyngitis cases in children are caused by GAS; meanwhile, 5 to 20% of pharyngitis in adults are streptococcal. The number of pharyngitis cases is higher in children than in adults due to exposures in schools, nurseries, and as a consequence of lower host immunity. Cases of Streptococcal pharyngitis occur more frequently in later winter to early spring in seasonal countries due to many people rebreathing the same indoor air. Disease cases are the lowest during autumn.
MT1 (metabolic type 1) clone is frequently associated with invasive ''Streptococcus pyogenes'' infections among developed countries. The incidence and mortality of ''S. pyogenes'' was high during the pre-penicillin era, but had already started to fall prior to the widespread availability of penicillin. Therefore, environmental factors do play a role in the ''S. pyogenes'' infection. Incidence of ''S. pyogenes'' is 2 to 4 per 100,000 population in developed countries and 12 to 83 per 100,000 population in developing countries. ''S. pyogenes'' infection is more frequently found in men than women, with highest rates in the elderly, followed by infants. In people with risk factors such as heart disease, diabetes, malignancy, blunt trauma, surgical incision, virus respiratory infection, including influenza, ''S. pyogenes'' infection happens in 17 to 25% of all cases. GAS secondary infection usually happens within one week of the diagnosis of influenza infection. In 14 to 16% of childhood ''S. pyogenes'' infections, there is a prior
chickenpox infection. Such ''S. pyogenes'' infection in children usually manifests as severe soft tissue infection with onset 4 to 12 days from the chickenpox diagnosis. There is also 40 to 60 times increase in risk of ''S. pyogenes'' infection within the first two weeks of chickenpox infection in children. However, 20 to 30% of ''S. pyogenes'' infection does occur in adults with no identifiable risk factors. The incidence is higher in children (50 to 80% of ''S. pyogenes'' infection) with no known risk factors. The rates of scarlet fever in UK was usually 4 in 100,000 population, however, in 2014, the rates had risen to 49 per 100,000 population. Rheumatic fever and rheumatic heart disease (RHD) usually occurs at 2 to 3 weeks after the throat infection, which is more common among the impoverished people in developing countries. From 1967 to 1996, the global mean incidence of rheumatic fever and RHD was 19 per 100,000 with the highest incidence at 51 per 100,000.
Maternal ''S. pyogenes'' infection usually happens in late pregnancy; at more than 30 weeks of gestation to four weeks postpartum, which accounts for 2 to 4% of all the ''S. pyogenes'' infections. This represents 20 to 100 times increase in risk for ''S. pyogenes'' infections. Clinical manifestations are: pneumonia, septic arthritis, necrotizing fasciitis, and genital tract sepsis. According to a study done by Queen Charlotte's hospital in London during the 1930s, the vagina was not the common source of such infection. On the contrary, maternal throat infection and close contacts with carriers were the more common sites for maternal ''S. pyogenes'' infection.
Bacteriology
Serotyping
In 1928,
Rebecca Lancefield
Rebecca Craighill Lancefield (January 5, 1895 – March 3, 1981). p.227 was a prominent American microbiologist. She joined the Rockefeller Institute for Medical Research (now Rockefeller University) in New York in 1918, and was associated with ...
published a method for serotyping ''S. pyogenes'' based on its cell-wall polysaccharide,
a
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 ...
factor displayed on its surface.
Later, in 1946, Lancefield described the serologic classification of ''S. pyogenes'' isolates based on their surface
T-antigen.
Four of the 20 T-antigens have been revealed to be
pili, which are used by bacteria to attach to host cells.
As of 2016, a total of 120 M proteins are identified. These M proteins are encoded by 234 types ''emm'' gene with greater than 1,200 alleles.
Lysogeny
All strains of ''S. pyogenes'' are polylysogenized, in that they carry one or more bacteriophage on their genomes.
Some of the 'phages may be defective, but in some cases active 'phage may compensate for defects in others.
In general, the genome of ''S. pyogenes'' strains isolated during disease are >90% identical, they differ by the 'phage they carry.
Virulence factors
''S. pyogenes'' has several
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 ...
factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers.
A carbohydrate-based
bacterial capsule
The bacteria capsule is a large structure common to many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily was ...
composed of
hyaluronic acid surrounds the bacterium, protecting it from
phagocytosis
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 ...
by
neutrophils.
In addition, the capsule and several factors embedded in the cell wall, including M protein,
lipoteichoic acid Lipoteichoic acid (LTA) is a major constituent of the cell wall of gram-positive bacteria. These organisms have an inner (or cytoplasmic) membrane and, external to it, a thick (up to 80 nanometer) peptidoglycan layer. The structure of LTA varies ...
, and protein F (SfbI) facilitate attachment to various host cells.
M protein also inhibits
opsonization
Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed (i.e. ...
by the alternative
complement pathway
A complement is something that completes something else.
Complement may refer specifically to:
The arts
* Complement (music), an interval that, when added to another, spans an octave
** Aggregate complementation, the separation of pitch-class ...
by binding to host complement regulators. The M protein found on some serotypes is also able to prevent opsonization by binding to
fibrinogen
Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood cl ...
.
However, the M protein is also the weakest point in this pathogen's defense, as
antibodies produced by the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
against M protein target the bacteria for engulfment by
phagocytes
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek '' ...
. M proteins are unique to each strain, and identification can be used clinically to confirm the strain causing an infection.
Genome
The genomes of different strains were sequenced (genome size is 1.8–1.9 Mbp) encoding about 1700-1900 proteins (1700 in strain NZ131,
1865 in strain MGAS5005
). Complete genome sequences of the type strain of ''S. pyogenes''
NCTC 8198TCCUG 4207T are available in
DNA Data Bank of Japan
The DNA Data Bank of Japan (DDBJ) is a biological database that collects DNA sequences. It is located at the National Institute of Genetics (NIG) in the Shizuoka prefecture of Japan. It is also a member of the International Nucleotide Sequence Da ...
,
European Nucleotide Archive
The European Nucleotide Archive (ENA) is a repository providing free and unrestricted access to annotated DNA and RNA sequences. It also stores complementary information such as experimental procedures, details of sequence assembly and other m ...
, and
GenBank
The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. It is produced and maintained by the National Center for Biotechnology Information (NCBI; a part ...
under the accession number
LN831034an
CP028841
Biofilm formation
Biofilms are a way for ''S. pyogenes,'' as well as other bacterial cells, to communicate with each other. In the biofilm gene expression for multiple purposes (such as defending against the host immune system) is controlled via
quorum sensing
In biology, quorum sensing or quorum signalling (QS) is the ability to detect and respond to cell population density by gene regulation. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at ...
.
One of the biofilm forming pathways in GAS is the Rgg2/3 pathway. It regulates SHP's (short hydrophobic peptides) that are quorum sensing pheromones a.k.a. autoinducers. The SHP's are translated to an immature form of the pheromone and must undergo processing, first by a metalloprotease enzyme inside the cell and then in the extracellular space, to reach their mature active form. The mode of transportation out of the cell and the extracellular processing factor(s) are still unknown. The mature SHP pheromone can then be taken into nearby cells and the cell it originated from via a transmembrane protein, oligopeptide permease.
In the cytosol the pheromones have two functions in the Rgg2/3 pathway. Firstly, they inhibit the activity of Rgg3 which is a transcriptional regulator repressing SHP production. Secondly, they bind another transcriptional regulator, Rgg2, that increases the production of SHP's, having an antagonistic effect to Rgg3. SHP's activating their own transcriptional activator creates a positive feedback loop, which is common for the production for quorum sensing peptides. It enables the rapid production of the pheromones in large quantities. The production of SHP's increases biofilm biogenesis.
It has been suggested that GAS switches between biofilm formation and degradation by utilizing pathways with opposing effects. Whilst Rgg2/3 pathway increases biofilm, the RopB pathway disrupts it. RopB is another Rgg-like protein (Rgg1) that directly activates SpeB (Streptococcal pyrogenic exotoxin B), a cysteine protease that acts as a virulence factor. In the absence of this pathway, biofilm formation is enhanced, possibly due to the lack of the protease degrading pheromones or other Rgg2/3 pathway counteracting effects.
Disease
''S. pyogenes'' is the cause of many human diseases, ranging from mild superficial skin infections to life-threatening systemic diseases.
[ Infections typically begin in the throat or skin. The most striking sign is a strawberry-like rash. Examples of mild ''S. pyogenes'' infections include ]pharyngitis
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a Rhinorrhea, runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a ...
(strep throat) and localized skin infection (impetigo
Impetigo is a bacterial infection that involves the superficial skin. The most common presentation is yellowish crusts on the face, arms, or legs. Less commonly there may be large blisters which affect the groin or armpits. The lesions may be pa ...
). Erysipelas
Erysipelas () is a relatively common bacterial infection of the superficial layer of the skin ( upper dermis), extending to the superficial lymphatic vessels within the skin, characterized by a raised, well-defined, tender, bright red rash, t ...
and 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 ...
are characterized by multiplication and lateral spread of ''S. pyogenes'' in deep layers of the skin. ''S. pyogenes'' invasion and multiplication in the fascia can lead to necrotizing fasciitis
Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or p ...
, a life-threatening condition which requires prompt surgical intervention to reduce morbidity and mortality. The bacterium is found in 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.
Infections due to certain strains of ''S. pyogenes'' can be associated with the release of bacterial toxin
A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...
s. Throat infections associated with release of certain toxins lead to scarlet fever
Scarlet fever, also known as Scarlatina, is an infectious disease caused by ''Streptococcus pyogenes'' a Group A streptococcus (GAS). The infection is a type of Group A streptococcal infection (Group A strep). It most commonly affects childr ...
. Other toxigenic ''S. pyogenes'' infections may lead to streptococcal toxic shock syndrome
Toxic shock syndrome (TSS) is a condition caused by bacterial toxins. Symptoms may include fever, rash, skin peeling, and low blood pressure. There may also be symptoms related to the specific underlying infection such as mastitis, osteomyeli ...
, which can be life-threatening.[
''S. pyogenes'' can also cause disease in the form of post-infectious "non-pyogenic" (not associated with local bacterial multiplication and pus formation) syndromes. These ]autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
-mediated complications follow a small percentage of infections and include rheumatic fever and acute post-infectious glomerulonephritis
Acute proliferative glomerulonephritis is a disorder of the small blood vessels of the kidney. It is a common complication of bacterial infections, typically skin infection by ''Streptococcus'' bacteria types 12, 4 and 1 (impetigo) but also afte ...
. Both conditions appear several weeks following the initial streptococcal infection. Rheumatic fever is characterized by inflammation of the joints and/or heart following an episode of streptococcal pharyngitis. Acute glomerulonephritis, inflammation of the renal
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
glomerulus
''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn".
''Glomerulus'' may refer to:
* the filter ...
, can follow streptococcal pharyngitis or skin infection.
This bacterium remains acutely sensitive to penicillin
Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
. Failure of treatment with penicillin is generally attributed to other local commensal organisms producing β-lactamase
Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapenems ...
, or failure to achieve adequate tissue levels in the pharynx. Certain strains have developed resistance to macrolides
The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macro ...
, tetracyclines
Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. T ...
, and clindamycin.
Vaccine
There is a polyvalent inactivated vaccine against several types of Streptococcus including S. pyogenes called " vacuna antipiogena polivalente BIOL" it is recommended an administration in a series of 5 weeks. Two weekly applications are made at intervals of 2 to 4 days. The vaccine is produced by the Instituto Biológico Argentino.
There is another potential vaccine being developed; the vaccine candidate peptide is called StreptInCor.
Applications
Bionanotechnology
Many ''S. pyogenes'' proteins have unique properties, which have been harnessed in recent years to produce a highly specific "superglue" and a route to enhance the effectiveness of antibody therapy.
Genome editing
The CRISPR system from this organism that is used to recognize and destroy DNA from invading viruses, thus stopping the infection, was appropriated in 2012 for use as a genome-editing tool that could potentially alter any piece of DNA and later RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
.
See also
* Friedrich Fehleisen
Friedrich Fehleisen () (1854–1924) was a German surgeon whose work focused on streptococcal bacteria. Dr. Fehleisen's work played a necessary role in the eventual uncovering of the etiology of many streptococcal illnesses. He made integral contri ...
* Friedrich Julius Rosenbach
Friedrich Julius Rosenbach, also known as Anton Julius Friedrich Rosenbach, (16 December 1842 – 6 December 1923) was a German physician and microbiologist. He is credited for differentiating ''Staphylococcus aureus'' and ''Staphylococcus albus'' ...
* Friedrich Loeffler
Friedrich August Johannes Loeffler (; 24 June 18529 April 1915) was a German bacteriologist at the University of Greifswald.
Biography
He obtained his M.D. degree from the University of Berlin in 1874. He worked with Robert Koch from 1879 to 1884 ...
* Frederick Twort
Frederick William Twort FRS (22 October 1877 – 20 March 1950) was an English bacteriologist and was the original discoverer in 1915 of bacteriophages (viruses that infect bacteria). He studied medicine at St Thomas's Hospital, London, was super ...
References
Further reading
*
*
*
*
*
* (corresponding summary article)
*
External links
Type strain of ''Streptococcus pyogenes'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
Nature-Inspired CRISPR Enzyme Discoveries Vastly Expand Genome Editing
On: SciTechDaily. June 16, 2020. Source: Media Lab, Massachusetts Institute of Technology.
{{DEFAULTSORT:Streptococcus Pyogenes
Streptococcaceae
Gram-positive bacteria
Pathogenic bacteria
Scarlet fever
Tonsil disorders
Bacteria described in 1884