A novel anti-virulence gene revealed by proteomic analysis in Shigella flexneri 2a.
BACKGROUND
Shigella flexneri is a gram-negative, facultative pathogen that causes the majority of communicable bacterial dysenteries in developing countries. The virulence factors of S. flexneri have been shown to be produced at 37 degrees C but not at 30 degrees C. To discover potential, novel virulence-related proteins of S. flexneri, we performed differential in-gel electrophoresis (DIGE) analysis to measure changes in the expression profile that are induced by a temperature increase.


RESULTS
The ArgT protein was dramatically down-regulated at 37 degrees C. In contrast, the ArgT from the non-pathogenic E. coli did not show this differential expression as in S. flexneri, which suggested that argT might be a potential anti-virulence gene. Competitive invasion assays in HeLa cells and in BALB/c mice with argT mutants were performed, and the results indicated that the over-expression of ArgTY225D would attenuate the virulence of S. flexneri. A comparative proteomic analysis was subsequently performed to investigate the effects of ArgT in S. flexneri at the molecular level. We show that HtrA is differentially expressed among different derivative strains.


CONCLUSIONS
Gene argT is a novel anti-virulence gene that may interfere with the virulence of S. flexneri via the transport of specific amino acids or by affecting the expression of the virulence factor, HtrA.
Zhao
Ge
G
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.|Shandong Eye Institute, Qingdao 266071, China.
Zhu
Li
L
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Feng
Erling
E
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Cao
Xiaoyu
X
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Shang
Na
N
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Liu
Xiankai
X
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Liao
Xiang
X
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Ying
Tianyi
T
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Wang
Jie
J
National Center of Biomedical Analysis, Beijing 100850, China.
Chen
Huipeng
H
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Wang
Hengliang
H
Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.