Inflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection.
Inflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection.
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DOI：
10.1016/j.chom.2016.08.013
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发表时间：
2016-10-12
影响因子：
30.3
通讯作者：
Hultgren SJ
中科院分区：
文献类型：
--
作者：
Conover MS;Ruer S;Taganna J;Kalas V;De Greve H;Pinkner JS;Dodson KW;Remaut H;Hultgren SJ
肾盂肾炎大肠大肠杆菌（UPEC）是尿路感染的主要原因，临床上被描述为膀胱炎。UPEC表达CUP皮利，CUP菌毛是具有粘附素的细胞外纤维，其结合泌尿道的粘膜表面。在这里，我们确定的作用，F9/Yde/Fml菌毛的UPEC的持久性在发炎的尿路上皮。Fml粘附素FmlH结合在核心-1和-2 O-聚糖中发现的半乳糖β1-3 N-乙酰半乳糖胺。在急性膀胱炎小鼠模型中，fmlH的缺失对UPEC毒力没有影响。然而，FmlH在慢性膀胱炎期间提供了适应性优势，慢性膀胱炎表现为持续性菌尿、高膀胱细菌负荷和慢性炎症。原位结合证实FmlH与发炎的膀胱紧密结合，但与未感染的膀胱不结合。根据其致病谱，用FmlH接种显著保护小鼠免受慢性膀胱炎。因此，UPEC采用单独的CUP皮利以适应膀胱感染期间快速变化的生态位。尿路致病性大肠杆菌（UPEC）表达细胞外，粘附尖端，纤维结合泌尿道粘膜表面。科诺菲尔等人表明，在持续的UPEC膀胱感染期间，尿路上皮糖组重塑诱导F9菌毛受体的出现，这使得F9菌毛介导的粘附、晚期定殖和慢性UTI成为可能。
Uropathogenic E. coli (UPEC) is the dominant cause of urinary tract infections, clinically described as cystitis. UPEC express CUP pili, which are extracellular fibers tipped with adhesins that bind mucosal surfaces of the urinary tract. Here we identify the role of the F9/Yde/Fml pilus for UPEC persistence in the inflamed urothelium. The Fml adhesin FmlH binds galactose β1-3 N-acetylgalactosamine found in core-1 and -2 O-glycans. Deletion of fmlH had no effect on UPEC virulence in an acute mouse model of cystitis. However, FmlH provided a fitness advantage during chronic cystitis, which is manifested as persistent bacteriuria, high bladder bacterial burdens and chronic inflammation. In situ binding confirmed that FmlH bound avidly to the inflamed, but not the naïve bladder. In accordance with its pathogenic profile, vaccination with FmlH significantly protected mice from chronic cystitis. Thus, UPEC employ separate CUP pili to adapt to the rapidly changing niche during bladder infection. Uropathogenic Escherichia coli (UPEC) express extracellular, adhesion-tipped, fibers that bind mucosal surfaces of the urinary tract. Conover et al. show that urothelial glycome remodeling during ongoing UPEC bladder infection induces the emergence of an F9 pilus receptor, which enables F9 pilus-mediated adherence, late stage colonization and chronic UTI.