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. 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. 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. 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.

中文翻译：

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cjrABC-senB 通过触发补体介导的杀伤作用阻碍血流中肠外致病性大肠杆菌的存活。


肠外致病性大肠杆菌 (ExPEC) 是一种常见的革兰氏阴性微生物，可引起各种感染，包括尿路感染 (UTI)、菌血症和新生儿脑膜炎。大肠杆菌的 cjrABC-senB 基因簇有助于 UTI 小鼠模型中的 ExPEC 毒力。一致地，cjrABC-senB 的分布在流行病学上与大肠杆菌引起的人类尿路感染相关。 cjrABC-senB 先前已被提议编码铁摄取系统，可能有助于 ExPEC 在铁可用性受限的尿道中存活。鉴于血液也是入侵细菌的铁限制环境，然而 cjrABC-senB 在 ExPEC 菌血症中的致病作用仍有待研究。评估了带有和不带有 cjrABC-senB 的 ExPEC RS218 菌株在小鼠血液和人血清中存活的能力。随后，评估了该基因簇在 ExPEC 与补体系统相互作用中的作用。最后，通过PCR测定了cjrABC-senB在人类临床大肠杆菌分离株中的分布。将与 UTI 无关的菌血症分离株（非 UTI 菌血症分离株）中的 cjrABC-senB 频率与 UTI 相关分离株和粪便分离株进行比较。 cjrABC-senB 的表达减弱了 RS218 在小鼠血液和人血清中的存活率。携带 cjrABC-senB 的菌株触发了增强的经典补体途径和替代补体途径激活，并且更容易受到血清中补体介导的杀伤。 cjrA 被确定为导致血清存活减弱的主要基因。 表达 cjrABC-senB 和 cjrA 会增加细菌对去污剂的敏感性并诱导周质蛋白渗漏，表明这些基因的表达会损害 ExPEC 外膜的完整性。此外，cjrABC-senB在非UTI菌血症分离株中的频率显着低于UTI相关分离株，而在非UTI菌血症分离株和粪便分离株中的频率无显着差异。一致地，这项流行病学调查表明 cjrABC-senB 不会导致人类大肠杆菌菌血症。 cjrABC-senB 对 ExPEC 发病机制的贡献是生态位依赖性且矛盾的，因为这些基因促进 ExPEC UTI 但阻碍菌血症。这种矛盾的生态位依赖性特征可能有利于针对大肠杆菌引起的感染的新策略的开发。