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

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posted on 2023-06-09, 00:07 authored by Ashraf Zarkan, Heather-Rose Macklyne, Andrew W Truman, Andrew R Hesketh, Hee-Jeon Hong
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Scientific Reports

ISSN

2045-2322

Publisher

Nature Publishing Group

Volume

6

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-25

First Open Access (FOA) Date

2016-01-25

First Compliant Deposit (FCD) Date

2016-01-25

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