Journal Article

The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II)

Abstract

Vancomycin is a front-line antibiotic used for the treatment of nosocomial infections, particularly those caused by methicillin-resistant Staphylococcus aureus. Despite its clinical importance the global effects of vancomycin exposure on bacterial physiology are poorly understood. In a previous transcriptomic analysis we identified a number of Zur regulon genes which were highly but transiently up-regulated by vancomycin in Streptomyces coelicolor. Here, we show that vancomycin also induces similar zinc homeostasis systems in a range of other bacteria and demonstrate that vancomycin binds to Zn(II) in vitro. This implies that vancomycin treatment sequesters zinc from bacterial cells thereby triggering a Zur-dependent zinc starvation response. The Kd value of the binding between vancomycin and Zn(II) was calculated using a novel fluorometric assay, and NMR was used to identify the binding site. These findings highlight a new biologically relevant aspect of the chemical property of vancomycin as a zinc chelator.

Attached files

Authors

Zarkan, A
Macklyne, H
Truman, A
Hesketh, A
Hong, H

Oxford Brookes departments

Faculty of Health and Life Sciences\Department of Biological and Medical Sciences

Dates

Year of publication: 2016
Date of RADAR deposit: 2016-06-30

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This work is licensed under a Creative Commons Attribution 4.0 International License

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Related resources

This RADAR resource is the Version of Record of The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II)
This RADAR resource is the Version of Record of The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II)