Nairn Brittany L, Lonergan Zachery R, Wang Jiefei, Braymer Joseph J, Zhang Yaofang, Calcutt M Wade, Lisher John P, Gilston Benjamin A, Chazin Walter J, de Crécy-Lagard Valerie, Giedroc David P, Skaar Eric P
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Cell Host Microbe. 2016 Jun 8;19(6):826-36. doi: 10.1016/j.chom.2016.05.007.
Zinc (Zn) is an essential metal that vertebrates sequester from pathogens to protect against infection. Investigating the opportunistic pathogen Acinetobacter baumannii's response to Zn starvation, we identified a putative Zn metallochaperone, ZigA, which binds Zn and is required for bacterial growth under Zn-limiting conditions and for disseminated infection in mice. ZigA is encoded adjacent to the histidine (His) utilization (Hut) system. The His ammonia-lyase HutH binds Zn very tightly only in the presence of high His and makes Zn bioavailable through His catabolism. The released Zn enables A. baumannii to combat host-imposed Zn starvation. These results demonstrate that A. baumannii employs several mechanisms to ensure bioavailability of Zn during infection, with ZigA functioning predominately during Zn starvation, but HutH operating in both Zn-deplete and -replete conditions to mobilize a labile His-Zn pool.
锌(Zn)是一种必需金属,脊椎动物会从病原体中摄取锌以预防感染。在研究机会致病菌鲍曼不动杆菌对锌饥饿的反应时,我们鉴定出一种假定的锌金属伴侣蛋白ZigA,它能结合锌,并且在锌限制条件下对细菌生长以及在小鼠体内的播散性感染都是必需的。ZigA与组氨酸(His)利用(Hut)系统相邻编码。组氨酸氨裂解酶HutH仅在高浓度组氨酸存在时才能非常紧密地结合锌,并通过组氨酸分解代谢使锌具有生物可利用性。释放出的锌使鲍曼不动杆菌能够对抗宿主造成的锌饥饿。这些结果表明,鲍曼不动杆菌采用多种机制来确保感染期间锌的生物可利用性,其中ZigA主要在锌饥饿期间发挥作用,而HutH在锌缺乏和充足的条件下均起作用,以调动不稳定的组氨酸-锌池。