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Insights into the antibacterial mechanism of action of chelating agents by selective deprivation of iron, manganese and zinc

Paterson, Joy R.; Beecroft, Marikka S.; Mulla, Raminder S.; Osman, Deenah; Reeder, Nancy L.; Caserta, Justin A.; Young, Tessa R.; Pettigrew, Charles A.; Davies, Gareth E.; Williams, J.A. Gareth; Sharples, Gary J.

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Joy Paterson
Post Doctoral Research Associate

Marikka S. Beecroft

Raminder S. Mulla

Deenah Osman

Nancy L. Reeder

Justin A. Caserta

Charles A. Pettigrew

Gareth E. Davies


Bacterial growth and proliferation can be restricted by limiting the availability of metal ions in their environment. Humans sequester iron, manganese and zinc to help prevent infection by pathogens, a system termed nutritional immunity. Commercially-used chelants have high binding affinities with a variety of metal ions, which may lead to antibacterial properties that mimic these innate immune processes. However, the modes of action of many of these chelating agents in bacterial growth inhibition and their selectivity in metal deprivation in cellulo remain ill-defined. We address this shortcoming by examining the effect of eleven chelators on Escherichia coli growth and their impact on the cellular concentration of five metals. Four distinct effects were uncovered: i) no apparent alteration in metal composition, ii) depletion of manganese alongside reductions in iron and zinc levels, iii) reduced zinc levels with a modest reduction in manganese, and iv) reduced iron levels coupled with elevated manganese. These effects do not correlate with the absolute known chelant metal ion affinities in solution, however, for at least five chelators for which key data are available, they can be explained by differences in the relative affinity of chelants for each metal ion. The results reveal significant insights into the mechanism of growth inhibition by chelants, highlighting their potential as antibacterials and as tools to probe how bacteria tolerate selective metal deprivation.

Journal Article Type Article
Acceptance Date Nov 9, 2021
Online Publication Date Nov 17, 2021
Publication Date 2022
Deposit Date Nov 22, 2021
Publicly Available Date Dec 7, 2021
Journal Applied and Environmental Microbiology
Print ISSN 0099-2240
Electronic ISSN 1098-5336
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Public URL


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