Pathogenic roles for CovS sensing acidic stress in group A streptococcus

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Streptococcus pyogenes (group A streptococcus, GAS) is an important human pathogen, causes mild and severe diseases such as pharyngitis, scarlet fever, cellulitis, necrotizing fasciitis, and toxic shock syndrome. Hyaluronic acid capsule is one of the bacterial virulence factors, involves in GAS invasion and resistance to phagocytic cell clearance. Clinical isolates with encapsulated phenotype is more virulent in mouse infection model than that of isolates without capsule over-expression. Genomic DNA sequencing analysis results indicate that the covR or covS mutation is responsible for the capsule over-expression. In laboratory condition, GAS could switch from normal to encapsulated morphology inside the infected mouse, indicating that the spontaneous mutation of the covR or covS gene is important for GAS adapting to host environment. CovR/S is the two-component regulatory system, which has been found to regulate about 15% genes expression in GAS. However, the underlying mechanism of the spontaneous covR or covS mutation in GAS adapting to host environment is still unknown. GAS clinical isolate A20 was used for infecting mouse subcutaneously, and the encapsulated strain with covS gene mutation (AP3) was recovered from spleen of the infected mouse. To compare with A20, AP3 was more resistant to acidic but not oxidative stress, and the hasA (hyaluronic acid capsule synthesis gene) expression of AP3 in pH 6.0 culture condition was de-repressed. Acidic stress is one of the environmental stresses when bacteria exposed to tissue inflammation and phagocytosis. These preliminary results suggest that the covS gene mutation would provide advantages for GAS escaping from innate immunity clearance. However, whether CovR/S involved in sensing and transducing acidic signal has not been addressed. In the present proposal, two specific aims will be addressed. First, to analyze whether CovS was responsible for sensing acidic signal and activating downstream CovR under acidic stress culture condition. Second, to elucidate whether acidic signal transduced by CovR/S was involved in GAS resistant to phagocytic clearance. To accomplish these specific aims, we’ll be able to understand the pathogensis of invasive GAS infection better, and to develop potential strategies for improving prognosis of invasive GAS infections.

Project IDs

Project ID:PC10111-0008
External Project ID:NSC101-2320-B182-044
Effective start/end date01/09/1231/08/13


  • Group A streptococcus
  • hyaluronic acid capsule
  • CovR/S
  • acidic stress
  • invasive infection


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