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Multi-target mode of action of silver against Staphylococcus aureus endows it with capability to combat antibiotic resistance
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Multi-target mode of action of silver against Staphylococcus aureus endows it with capability to combat antibiotic resistance
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Journal Article
Multi-target mode of action of silver against Staphylococcus aureus endows it with capability to combat antibiotic resistance
2021
Overview
The rapid emergence of drug resistant
Staphylococcus aureus
(
S. aureus
) poses a serious threat to public health globally. Silver (Ag)-based antimicrobials are promising to combat antibiotic resistant
S. aureus
, yet their molecular targets are largely elusive. Herein, we separate and identify 38 authentic Ag
+
-binding proteins in
S. aureus
at the whole-cell scale. We then capture the molecular snapshot on the dynamic action of Ag
+
against
S. aureus
and further validate that Ag
+
could inhibit a key target 6-phosphogluconate dehydrogenase through binding to catalytic His185 by X-ray crystallography. Significantly, the multi-target mode of action of Ag
+
(and nanosilver) endows its sustainable antimicrobial efficacy, leading to enhanced efficacy of conventional antibiotics and resensitization of MRSA to antibiotics. Our study resolves the long-standing question of the molecular targets of silver in
S. aureus
and offers insights into the sustainable bacterial susceptibility of silver, providing a potential approach for combating antimicrobial resistance.
Silver (Ag) has been used as an antimicrobial agent since a long time, but its molecular mechanism of action was not elucidated due to technical challenges. Here, the authors develop a mass spectrometric approach to identify the Ag-proteome in
Staphylococcus aureus
, and capture a molecular snapshot of the dynamic bactericidal mode of action of Ag through targeting multiple biological pathways.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/31
/ 140/146
/ 38/88
/ 82/80
/ 82/83
/ Anti-Bacterial Agents - pharmacology
/ Binding
/ Drug Resistance, Bacterial - drug effects
/ Humanities and Social Sciences
/ Metal Nanoparticles - chemistry
/ Methicillin-Resistant Staphylococcus aureus
/ Phosphogluconate dehydrogenase (decarboxylating)
/ Phosphogluconate Dehydrogenase - drug effects
/ Science
/ Silver
