In preparing this paper we reviewed articles in the Medline database for “Streptococcus pyogenes”, with special attention to “pathogenesis”, “genetics”, and “virulence”. In addition, we reviewed the bibliographies of previously published articles and reviews relating to the topics discussed herein. Papers included in the review were selected for scientific quality and relevance to the topic.
ReviewMolecular basis of group A streptococcal virulence
Section snippets
M protein
The major human host defence against invasive GAS infection is that of phagocytosis and killing by polymorphonuclear leucocytes (PML). Thus, a critical somatic GAS virulence factor is an antiphagocytic surface constituent known as M protein.
The structural basis of the biological properties of M protein has been elucidated over the past three decades.2, 3 M protein is composed of two polypeptide chains complexed in an alpha-helical coiled-coil configuration anchored in the cell membrane,
The streptococcal genome
In little over a year the complete genome sequences from three S pyogenes types, M1,109 M3,110 and M18,111 have been reported. GAS serotypes may be associated with distinct clinical syndromes, with M1 and M3 frequently isolated from cases of necrotising fasciitis and STSS, and M18 strains associated with the epidemic of acute rheumatic fever seen in the Salt Lake City area since the mid 1980s. This genome information provides insight into the subtle genetic differences between streptococcal
Genetic regulation of streptococcal virulence factors
Control of the expression of the described virulence factors over time and under diverse environmental circumstances depends on a complex system of genetic modulation. Of the known transcriptional regulators in GAS, the two most intensively studied are Mga113 (multiple gene regulator), the regulator of M protein expression, and a two-component regulatory system known as CsrRS114 (capsule synthesis regulator) or alternatively, CovRS115 (“control of virulence genes”), which represses the
Acute rheumatic fever
The development of acute rheumatic fever (ARF) requires antecedent infection with a specific organism, the GAS, at a specific body site, the upper respiratory tract. Although the exact mechanism by which GAS induces the disease remains unexplained, most attention has been focused on the notion of autoimmunity, or, more precisely, molecular mimicry. This theory is rendered more credible by several examples of antigenic similarity between somatic constituents of GAS and human tissues, including
Acute glomerulonephritis
Acute poststreptococcal glomerulonephritis (APSGN) follows infection with a limited number of GAS serotypes. Type 12 is the most frequent M serotype causing APSGN after pharyngitis or tonsillitis, whereas M-49 is the type most frequently related to pyoderma-associated nephritis. Not all streptococcal strains belonging to these serotypes are nephritogenic, however. There are no reliable biological markers to differentiate nephritogenic from nonnephritogenic streptococci. APSGN is almost always
Prospects for a group A streptococcal vaccine
The persistence of rheumatic fever in many developing countries of the world, the apparent increase in life-threatening invasive GAS infections in North America and Europe, and the revolution in molecular biology have spurred attempts to achieve a long-sought goal: a safe and effective vaccine against the GAS. The most promising approaches are M protein-based and include multivalent type-specific vaccines146, 147 and those directed at non-type specific, highly conserved portions of the molecule.
Search strategy and selection criteria
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