The Yersiniabactin-Associated ATP Binding Cassette Proteins YbtP and YbtQ Enhance Escherichia coli Fitness during High-Titer Cystitis

The Yersiniabactin-Associated ATP Binding Cassette Proteins YbtP and YbtQ Enhance Escherichia coli Fitness during High-Titer Cystitis
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DOI:
10.1128/iai.01211-15
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发表时间:
2016-05-01
影响因子:
3.1
通讯作者:
Henderson, Jeffrey P.
Henderson, Jeffrey P.
中科院分区:
医学2区
文献类型:
--
作者:
Koh, Eun-Ik;Hung, Chia S.;Henderson, Jeffrey P.

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耶尔森氏菌高致病性岛(HPI)是与尿路感染(UTI)相关的大肠埃希菌菌株所使用的多种毒力策略的共同点。在这个岛上的基因是ybtP和ybtQ,编码独特的ATP结合盒(ABC)蛋白与铁(III)-耶尔森氏杆菌素进口鼠疫耶尔森氏菌。在这项研究中,我们比较了ybtPQ对模型E的影响。大肠杆菌膀胱炎菌株在体外培养和实验小鼠感染。在标准培养条件下,ybtPQ无效突变体没有表现出生长缺陷,与该背景下的非必需性一致。在铁(III)-耶尔森氏单抗依赖性生长过程中,观察到生长缺陷表型,并在体外进行遗传补充。在接种到C3 H/HEN和C3 H/HeOuJ小鼠的膀胱中后,该菌株在进展为高滴度膀胱感染的小鼠亚组中表现出深刻的106倍竞争性感染缺陷。这些结果确定了YbtPQ在高滴度膀胱炎的高度炎症微环境特征中的毒力作用。这种严重的竞争缺陷可能与耶尔森氏菌对HPI阳性大肠杆菌的明显选择有关。大肠埃希菌感染。
The Yersinia high-pathogenicity island (HPI) is common to multiple virulence strategies used by Escherichia coli strains associated with urinary tract infection (UTI). Among the genes in this island are ybtP and ybtQ, encoding distinctive ATP binding cassette (ABC) proteins associated with iron(III)-yersiniabactin import in Yersinia pestis. In this study, we compared the impact of ybtPQ on a model E. coli cystitis strain during in vitro culture and experimental murine infections. A ybtPQ-null mutant exhibited no growth defect under standard culture conditions, consistent with nonessentiality in this background. A growth defect phenotype was observed and genetically complemented in vitro during iron(III)-yersiniabactin-dependent growth. Following inoculation into the bladders of C3H/HEN and C3H/HeOuJ mice, this strain exhibited a profound, 106-fold competitive infection defect in the subgroup of mice that progressed to high-titer bladder infections. These results identify a virulence role for YbtPQ in the highly inflammatory microenvironment characteristic of high-titer cystitis. The profound competitive defect may relate to the apparent selection of Yersinia HPI-positive E. coli in uncomplicated clinical UTIs.