The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II)
Truman, Andrew W
Nature Publishing Group
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Zarkan, A., Macklyne, H., Truman, A. W., Hesketh, A., & Hong, H. (2016). The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II). Scientific Reports, 6 (19602)https://doi.org/10.1038/srep19602
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.
This work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research Council, UK (G0700141). A.Z. was supported from the Said foundation and Cambridge Trust.
External DOI: https://doi.org/10.1038/srep19602
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252998