Serotype-Specifc Virulence Factor Expression and Regulation in the Group A Streptococcus
Biochemistry and Molecular Biology
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The group A Streptococcus (GAS) is a Gram-positive human obligate pathogen, and is capable of causing perhaps the most diverse array of clinical manifestations of any known pathogen. Disease states range from mild and typically self-limiting phayngeal infections (the canonical "strep throat") through the permanent cardiac damage of rheumatic heart disease and the often fatal necrotizing fasciitis (the "flesh-eating" disease). Although not considered a primary threat in most developed countries, the burden of GAS disease around the globe amounts to greater than half a million deaths every year. Disconcertingly, recent public health data indicates the burden of GAS in the United States is climbing, with rates of both rheumatic heart disease and maternal sepsis on the rise, especially across the "Black Belt" of the American South. Although there are many factors contributing to this increase in documented GAS infections, one significant reason is the lack of a licensed preventative vaccine. This is due partly to the fact that GAS is both polygenic and polymorphic, displaying phenotypic differences among serotypes, and there are few proteins which are expressed by the majority of GAS strains. There are, however, several candidate vaccines under development which utilize different cell-surface GAS proteins to provoke protective immunity, and this study focuses on the regulation of the expression of several such virulence factors. This project is the first to demonstrate serotype-specific regulation by an sRNA in GAS, and has identified a serotype-specific basis for the expression of pilus. We have characterized the molecular mechanisms underlying this regulation, and are first to provide evidence an sRNA directly contributes to virulence in GAS.