Streptococcus pyogenes

Typing Services
Spy-emm
Spy-sclB

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Streptococcus pyogenes (Group A strep; GAS) is a common cause of two relatively mild illnesses, phyaryngitis (occasionally presenting as scarlet fever) and impetigo.  It is also among the normal respiratory tract, throat, or skin flora of 5-15% of healthy individuals (highest in children).  On the other hand, when host defenses are compromised (e.g., through chronic illness or steroid use), and this beta-hemolytic gram positive bacterium gains access to normally sterile sites, S. pyogenes infection can be life threatening.  These invasive GAS diseases, which are strain-dependent to varying extents, include necrotizing fasciitis (“flesh-eating bacteria”) and streptococcal toxic shock syndrome (distinct from staphylococcal toxic shock syndrome associated with tampon use).  S. pyogenes infection is also notable for its occasional autoimmune sequelae, specifically acute rheumatic fever (inflammation of the joints and/or heart following streptococcal pharyngitis) and acute postinfectious glomerulonephritis (inflammation of the renal glomerulus following streptococcal pharyngitis or skin infection).  More controversial is PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections).

S. pyogenes is highly contagious, typically transmitted through direct or indirect contact with mucus from pharyngitis patients or skin sores from those with impetigo.  Fortunately, S. pyogenes remains highly susceptible to penicillin, and treatment greatly reduces the risk of transmission to others.  Nevertheless, outbreaks of invasive or non-invasive infection continue to occur, particularly in healthcare workers exposed to GAS patients or in residents of long-term care facilities.

 

Rapid strep tests are typically used to detect S. pyogenes, but negative results require confirmation by culture, which has higher sensitivity and hence remains the diagnostic gold standard.

In addition to hemolysins, an antiphagocytic capsule, and strain-specific superantigens and toxins, virulence factors include M protein, a polymorphic cell wall component that contributes to host cell adherence and inhibits opsonization by binding to complement pathway regulators and, in some strains, by binding fibrinogen.  M protein is also a major target for protective antibodies, and consequently has been a major focus of vaccine development, although autoimmunity is a clear concern.

 

Moreover, M protein represents the primary basis for S. pyogenes strain typing.  The original Lancefield M protein serotypes have, in recent years, been greatly expanded through DNA sequence analysis of its gene, emm (www.cdc.gov/ncidod/biotech/strep/M-ProteinGene_typing.htm).  Over 100 emm types (and many additional subtypes and unnamed sequence types) have been defined; 25 of these types are responsible for 90% of GAS disease in North America and Europe.  Outbreaks typically involve emm type 1, although types 3, 11, 59, and 81 have also been recently implicated.  Furthermore, specific emm types have predilections for throat versus skin.  An active area of research is elucidating the strain differences responsible for invasive versus non-invasive disease.

MicrobiType services for S. pyogenes surveillance and outbreak investigation include Spy-emm and Spy-sclB.  The former is a genomics-optimized modification of the CDC protocol, and takes advantage of the large emm database and long-appreciated central role of M protein in S. pyogenes disease, immunity, and epidemiology.  The results delivered are emm type (e.g., emm 1.0) and sequence alignment.  The latter service, Spy-sclB, addresses the limitation of emm typing: its modest resolution.  Through sequence analysis of the highly polymorphic repeat region of sclB (encoding a collagen-like protein), independent isolates sharing the same emm type are readily resolved (see Spy-sclB dendrogram with emm types).  The result delivered is a similar dendrogram and sequence alignment showing the relationship of your isolate to database strains, and to additional isolates submitted concurrently or previously from your lab.

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