Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Microbe-Host Interactions Training Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Infect Immun. 2019 Nov 18;87(12). doi: 10.1128/IAI.00746-19. Print 2019 Dec.
is an opportunistic bacterial pathogen capable of causing a variety of infections, including pneumonia, sepsis, wound, and burn infections. is an increasing threat to public health due to the prevalence of multidrug-resistant strains, leading the World Health Organization to declare a "Priority 1: Critical" pathogen, for which the development of novel antimicrobials is desperately needed. Zinc (Zn) is an essential nutrient that pathogenic bacteria, including , must acquire from their hosts in order to survive. Consequently, vertebrate hosts have defense mechanisms to sequester Zn from invading bacteria through a process known as nutritional immunity. Here, we describe a ptake (Znu) system that enables to overcome this host-imposed Zn limitation. The Znu system consists of an inner membrane ABC transporter and an outer membrane TonB-dependent receptor. Strains of lacking any individual Znu component are unable to grow in Zn-starved conditions, including in the presence of the host nutritional immunity protein calprotectin. The Znu system contributes to Zn-limited growth by aiding directly in the uptake of Zn into cells and is important for pathogenesis in murine models of infection. These results demonstrate that the Znu system allows to subvert host nutritional immunity and acquire Zn during infection.
是一种机会性细菌病原体,能够引起多种感染,包括肺炎、败血症、伤口和烧伤感染。由于多药耐药菌株的流行,对公共健康构成了日益严重的威胁,世界卫生组织宣布为“优先 1:关键”病原体,因此迫切需要开发新型抗菌药物。锌(Zn)是一种必需的营养物质,包括,必须从宿主中获取才能生存。因此,脊椎动物宿主通过一种称为营养免疫的过程来从入侵细菌中隔离 Zn。在这里,我们描述了一种 ptake(Znu)系统,使能够克服这种宿主施加的 Zn 限制。Znu 系统由内膜 ABC 转运蛋白和外膜 TonB 依赖性受体组成。缺乏任何单个 Znu 成分的株系都无法在 Zn 饥饿条件下生长,包括在存在宿主营养免疫蛋白钙卫蛋白的情况下。Znu 系统通过直接帮助将 Zn 摄取到细胞中来促进 Zn 限制生长,并且在感染的小鼠模型中对发病机制很重要。这些结果表明,Znu 系统允许在感染期间颠覆宿主的营养免疫并获取 Zn。