- 作者: Wen-Chun Huang, Yi-Jyun Liao, Masayuki Hashimoto, Kuan-Fu Chen, Chishih Chu, Po-Chuen Hsu, Shuying Wang and Ching-Hao Teng
- 作者服務機構: 1. Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, 4th F, 367 Sheng Li Road, North District, Tainan City, Taiwan 2. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan 3. Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan City, Taiwan 4. Department of Microbiology, Immunology, and Biopharmaceuticals, National Chiayi University, Chiayi City, Taiwan 5. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan 6. Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan City, Taiwan 7. Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan City, Taiwan
- 中文摘要:
- 英文摘要:
Background
Extraintestinal pathogenic E. coli (ExPEC) is a common gram-negative organism causing various infections, including urinary tract infections (UTIs), bacteremia, and neonatal meningitis. The cjrABC-senB gene cluster of E. coli contributes to ExPEC virulence in the mouse model of UTIs. Consistently, the distribution of cjrABC-senB is epidemiologically associated with human UTIs caused by E. coli. cjrABC-senB, which has previously been proposed to encode an iron uptake system, may facilitate ExPEC survival in the iron availability-restricted urinary tract. Given that the bloodstream is also an iron limited environment to invading bacteria, the pathogenic role of cjrABC-senB in ExPEC bacteremia, however, remains to be investigated.
Methods
The ability of ExPEC RS218 strains with and without cjrABC-senB to survive in the mouse bloodstream and human serum was evaluated. Subsequently, the role of this gene cluster in the ExPEC interaction with the complement system was evaluated. Finally, the distribution of cjrABC-senB in human clinical E. coli isolates was determined by PCR. The frequency of cjrABC-senB in bacteremia isolates that were not associated with UTIs (non-UTI bacteremia isolates) was compared with that in UTI-associated isolates and fecal isolates.
Results
Expression of cjrABC-senB attenuated the survival of RS218 in the mouse bloodstream and human serum. The cjrABC-senB-harboring strains triggered enhanced classical- and alternative-complement pathway activation and became more vulnerable to complement-mediated killing in serum. cjrA was identified as the major gene responsible for the attenuated serum survival. Expressing cjrABC-senB and cjrA increased bacterial susceptibility to detergent and induced periplasmic protein leakage, suggesting that the expression of these genes compromises the integrity of the outer membrane of ExPEC. In addition, the frequency of cjrABC-senB in non-UTI bacteremia isolates was significantly lower than that in UTI-associated isolates, while the frequencies in non-UTI bacteremia isolates and fecal isolates showed no significant difference. Consistently, this epidemiological investigation suggests that cjrABC-senB does not contribute to E. coli bacteremia in humans.
Conclusion
The contribution of cjrABC-senB to the pathogenesis of ExPEC is niche dependent and contradictory because the genes facilitate ExPEC UTIs but hinder bacteremia. The contradictory niche-dependent characteristic may benefit the development of novel strategies against E. coli-caused infections. - 中文關鍵字:
- 英文關鍵字: Extraintestinal pathogenic E. coli, cjrA, cjrB, cjrC, senB, cjrABC-senB, ExPEC, Urinary tract infections, Bacteremia