Inetwork integration raminder12/16/2023 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. 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 following 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. We address this shortcoming by examining the effect of 11 chelators on Escherichia coli growth and their impact on the cellular concentration of five metals. 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. 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. Humans sequester iron, manganese, and zinc to help prevent infection by pathogens, a system termed nutritional immunity. Bacterial growth and proliferation can be restricted by limiting the availability of metal ions in their environment.
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