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质粒增强了尿路感染病原体鲍曼不动杆菌染色体基因的尿路定植。

Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes.

机构信息

Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, 63110, USA.

Department of Molecular Microbiology, Center for Women's Infectious Disease Research, Washington University School of Medicine, St Louis, MO, 63110, USA.

出版信息

Nat Commun. 2019 Jun 24;10(1):2763. doi: 10.1038/s41467-019-10706-y.

Abstract

Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries the plasmid pAB5, a member of the family of large conjugative plasmids that represses the type VI secretion system (T6SS) in multiple Acinetobacter strains. pAB5 confers niche specificity, as its carriage improves UPAB1 survival in a CAUTI model and decreases virulence in a pneumonia model. Comparative proteomic and transcriptomic analyses show that pAB5 regulates the expression of multiple chromosomally-encoded virulence factors besides T6SS. Our results demonstrate that plasmids can impact bacterial infections by controlling the expression of chromosomal genes.

摘要

耐多药(MDR)鲍曼不动杆菌对全球健康构成日益严重的威胁。关于鲍曼不动杆菌发病机制的研究主要集中在肺炎和血流感染上,尽管五分之一的鲍曼不动杆菌菌株是从尿源分离出来的。在这项研究中,我们强调了鲍曼不动杆菌作为尿病原体的作用。我们使用 UPAB1 开发了第一个鲍曼不动杆菌导管相关尿路感染(CAUTI)的小鼠模型,UPAB1 是最近从尿液中分离出来的多药耐药株。UPAB1 携带质粒 pAB5,这是一类大型可转移质粒家族的成员,该质粒抑制多种不动杆菌菌株中的 VI 型分泌系统(T6SS)。pAB5 赋予了特定的生态位,因为它的携带可以提高 UPAB1 在 CAUTI 模型中的存活率,并降低在肺炎模型中的毒力。比较蛋白质组学和转录组学分析表明,pAB5 除了 T6SS 之外,还调节多个染色体编码毒力因子的表达。我们的结果表明,质粒可以通过控制染色体基因的表达来影响细菌感染。

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