Project Details
Abstract
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
External Project ID:NSC101-2320-B182-044
Status | Finished |
---|---|
Effective start/end date | 01/09/12 → 31/08/13 |
Keywords
- Group A streptococcus
- hyaluronic acid capsule
- CovR/S
- acidic stress
- invasive infection
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