NhaA facilitates the maintenance of bacterial envelope integrity and the evasion of complement attack contributing to extraintestinal pathogenic Escherichia coli virulence
文献类型： 外文期刊
作者： Mao, Zhao 1 ; Zhang, Haobo 2 ; Cai, Wentong 1 ; Yang, Yan 1 ; Zhang, Xinyang 1 ; Jiang, Fengwei 1 ; Li, Ganwu 1 ;
作者机构： 1.Chinese Acad Agr Sci, Harbin Vet Res Inst, Key Lab Vet Publ Hlth, State Key Lab Vet Biotechnol,Minist Agr, Harbin, Peoples R China
2.China Anim Hlth & Epidemiol Ctr, Div Zoonoses Surveillance, Natl Anim TB Reference Lab, Qingdao, Peoples R China
3.Iowa State Univ, Coll Vet Med, Dept Vet Diagnost & Prod Anim Med, Ames, IA 50011 USA
关键词： NhaA; ExPEC; virulence; envelope integrity; complement system; serum resistance
期刊名称：INFECTION AND IMMUNITY （ 影响因子：3.1； 五年影响因子：3.2 ）
ISSN： 0019-9567
年卷期： 2023 年
页码：
收录情况： SCI
摘要： Extraintestinal pathogenic Escherichia coli (ExPEC) is responsible for severe bloodstream infections in humans and animals. However, the mechanisms underlying ExPEC's serum resistance remain incompletely understood. Through the transposondirected insertion-site sequencing approach, our previous study identified nhaA, the gene encoding a Na+/H+ antiporter, as a crucial factor for infection in vivo. In this study, we investigated the role of NhaA in ExPEC virulence utilizing both in vitro models and systemic infection models involving avian and mammalian animals. Genetic mutagenesis analysis revealed that nhaA deletion resulted in filamentous bacterial morphology and rendered the bacteria more susceptible to sodium dodecyl sulfate, suggesting the role of nhaA in maintaining cell envelope integrity. The nhaA mutant also displayed heightened sensitivity to complement-mediated killing compared to the wild-type strain, attributed to augmented deposition of complement components (C3b and C9). Remarkably, NhaA played a more crucial role in virulence compared to several well-known factors, including Iss, Prc, NlpI, and OmpA. Our findings revealed that NhaA significantly enhanced virulence across diverse human ExPEC prototype strains within B2 phylogroups, suggesting widespread involvement in virulence. Given its pivotal role, NhaA could serve as a potential drug target for tackling ExPEC infections.
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