The Response of Acinetobacter baumannii to Zinc Starvation

Brittany L. Nairn, Zachery R. Lonergan, Jiefei Wang, Joseph J. Braymer, Yaofang Zhang, M. Wade Calcutt, John P. Lisher, Benjamin A. Gilston, Walter J. Chazin, Valerie De Crécy-Lagard, David P. Giedroc, Eric P. Skaar

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)826-836
Number of pages11
JournalCell Host and Microbe
Volume19
Issue number6
DOIs
StatePublished - Jun 8 2016

Bibliographical note

Funding Information:
Work presented in this manuscript was supported by grants R01 AI1091771, R01 AI101171, and R01 GM042569 from the NIH. B.L.N. was supported by grant F32 AI108192 from the NIAID and the Childhood Infection Research Program T32 AI095202. Z.R.L. is supported by the Training Program in Environmental Toxicology T32 ES007028. V.d.C.-L. is supported by the grant R01 GM70641 from the NIH. The content of this article does not necessarily represent the views of the NIH or NIAID and is solely the responsibility of the authors.

Publisher Copyright:
© 2016 Elsevier Inc.

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