Streptococcus pyogenes

Streptococcus pyogenes
False-color scanning electron micrograph of chain of Streptococcus pyogenes bacteria (yellow)
Scientific classification
Domain:	Bacteria
Phylum:	Bacillota
Class:	Bacilli
Order:	Lactobacillales
Family:	Streptococcaceae
Genus:	Streptococcus
Species:	S. pyogenes
Binomial name
Streptococcus pyogenes Rosenbach 1884

Streptococcus pyogenes is a

The species name is derived from Greek words meaning 'a chain' (streptos) of berries (coccus [Latinized from kokkos]) and pus (pyo)-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. Staphylococci are catalase positive whereas streptococci are catalase-negative.^[2] S. pyogenes can be cultured on fresh blood agar plates. The PYR test allows for the differentiation of Streptococcus pyogenes from other morphologically similar beta-hemolytic streptococci (including S. dysgalactiae subsp. esquismilis) as S. pyogenes will produce a positive test result.^[3]

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, and these cases have a mortality rate of 25%.^[4] Early recognition and treatment are critical; diagnostic failure can result in sepsis and death.^[5][6] S. pyogenes is clinically and historically significant as the cause of scarlet fever, which results from exposure to the species' exotoxin.^[7]

Epidemiology

Unlike most bacterial pathogens, S. pyogenes only infects humans. Thus, zoonotic transmission from an animal (or animal products) to a human is rare.^[8]

S. pyogenes typically colonizes the throat, genital mucosa, rectum, and skin. Of healthy adults, 1% to 5% have throat, vaginal, or rectal carriage, with children being more common carriers. Most frequently, transmission from one person to another occurs due to inhalation of respiratory droplets, produced by sneezing and coughing from an infected person. Skin contact, contact with objects harboring the bacterium, and consumption of contaminated food are possible but uncommon modes of transmission. Streptococcal pharyngitis occurs most frequently in late winter to early spring in most countries as indoor spaces are used more often and thus more crowded. Disease cases are the lowest during autumn.^[9]

Maternal S. pyogenes infection usually happens in late pregnancy, at more than 30 weeks of gestation to four weeks postpartum. Maternal infections account for 2 to 4% of all clinically diagnosed S. pyogenes infections.^[9] The risk of sepsis is relatively high compared to other bacterial infections acquired during pregnancy, and S. pyogenes is a leading cause of septic shock and death in pregnant and postpartum women.^[10]

Bacteriology

Serotyping

In 1928, Rebecca Lancefield published a method for serotyping S. pyogenes based on its cell-wall polysaccharide,^[11] a virulence factor displayed on its surface.^[12] Later, in 1946, Lancefield described the serologic classification of S. pyogenes isolates based on components of their surface pili (known as the T-antigen)^[13] which are used by bacteria to attach to host cells.^[14] 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.^[9]

Lysogeny

All strains of S. pyogenes are polylysogenized, in that they carry one or more bacteriophage on their genomes.^[15] Some of the 'phages may be defective, but in some cases active 'phage may compensate for defects in others.^[16] In general, the genome of S. pyogenes strains isolated during disease are >90% identical, they differ by the 'phage they carry.^[17]

Virulence factors

S. pyogenes has several

The genomes of different strains were sequenced (genome size is 1.8–1.9 Mbp)[28] encoding about 1700-1900 proteins (1700 in strain NZ131,^[29][30] 1865 in strain MGAS5005^[31][32]). Complete genome sequences of the type strain of S. pyogenes (NCTC 8198^T = CCUG 4207^T) are available in DNA Data Bank of Japan, European Nucleotide Archive, and GenBank under the accession numbers LN831034 and CP028841.^[33]

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.^[34] 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.^[34] 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.^[34] 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.^[34]

Disease

S. pyogenes is the cause of many human diseases, ranging from mild superficial skin infections to life-threatening systemic diseases.^[2] The most frequent manifestations of disease are commonly known as scarlet fever. 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 (strep throat) and localized skin infection (impetigo). Erysipelas and cellulitis are characterized by multiplication and lateral spread of S. pyogenes in deep layers of the skin. S. pyogenes invasion and multiplication in the fascia beneath the skin can lead to necrotizing fasciitis, a life-threatening surgical emergency.^[35][36] The bacterium is also an important cause of infection in newborns, who are susceptible to some forms of the infection that are rarely seen in adults, including meningitis.^[37][38]

Like many pathogenic bacteria, S. pyogenes may colonize a healthy person's respiratory system without causing disease. It is commonly found in some populations as part of the mixed microbiome of the upper respiratory tract. Individuals who have the bacterium in their bodies but no signs of disease are known as asymptomatic carriers. The bacteria may start to cause disease when the host's immune system weakens, such as during a viral respiratory infection, which may lead to S. pyogenes superinfection.^[39][40]

S. pyogenes infections are commonly associated with the release of one or more bacterial toxins. The release of endotoxins from throat infections has been linked to the development of scarlet fever.^[7] Other toxins produced by S. pyogenes may lead to streptococcal toxic shock syndrome, a life-threatening emergency.^[2]

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

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.[42]

There is another potential vaccine being developed; the vaccine candidate peptide is called StreptInCor.^[43]

Applications

Bionanotechnology

Many S. pyogenes proteins have unique properties, which have been harnessed in recent years to produce a highly specific "superglue"^[44][45] and a route to enhance the effectiveness of antibody therapy.^[46]

Genome editing

The CRISPR system from this organism^[47] 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.^[48]

See also

• Friedrich Fehleisen
• Friedrich Julius Rosenbach
• Friedrich Loeffler
• Frederick Twort

References