Xie Yi, Yao Yufeng, Kolisnychenko Vitaliy, Teng Ching-Hao, Kim Kwang Sik
Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 600 North Wolfe St., Park 256, Baltimore, MD 21287, USA.
Infect Immun. 2006 Jul;74(7):4039-47. doi: 10.1128/IAI.02058-05.
Type 1 fimbriae have been suggested to play a role in the pathogenesis of extraintestinal Escherichia coli infection. Type 1 fimbriation in E. coli is phase variable and known to be dependent upon FimB and FimE, the two recombinases that invert the molecular switch fimS and control the expression of the downstream fim operon. Here we showed that HbiF, a novel site-specific recombinase, inverted fimS independently of FimB and FimE. HbiF-mediated fimS inversion appeared to be predominantly switching from "off" (termed OFF) to "on" (termed ON) orientation. This is different from the fimS inversion mediated by either FimB (bidirectional ON to OFF and OFF to ON) or FimE (unidirectional ON to OFF). Constitutive expression of the hbiF gene in E. coli resulted in a fimS-locked-ON phenotype, which resulted in the pathogenic E. coli K1 strain being incapable of inducing a high degree of bacteremia in neonatal rats. Discovery of HbiF-mediated OFF-to-ON fimS switching provides a new opportunity to develop a strategy for the prevention and therapy of extraintestinal E. coli infection including bacteremia and meningitis.
1型菌毛已被认为在肠外大肠杆菌感染的发病机制中起作用。大肠杆菌中的1型菌毛形成具有相变特性，已知其依赖于FimB和FimE这两种重组酶，它们可使分子开关fimS发生倒位并控制下游fim操纵子的表达。在此我们表明，新型位点特异性重组酶HbiF可独立于FimB和FimE使fimS发生倒位。HbiF介导的fimS倒位似乎主要是从“关闭”（称为OFF）方向转变为“开启”（称为ON）方向。这与由FimB（双向的ON到OFF和OFF到ON）或FimE（单向的ON到OFF）介导的fimS倒位不同。在大肠杆菌中组成型表达hbiF基因会导致fimS锁定为ON的表型，这使得致病性大肠杆菌K1菌株无法在新生大鼠中诱导高度菌血症。HbiF介导的fimS从OFF到ON的转换的发现为制定预防和治疗包括菌血症和脑膜炎在内的肠外大肠杆菌感染的策略提供了新机会。
