``On demand'' redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor

Shukla, Prashant and Khodade, Vinayak S and SharathChandra, Mallojjala and Chauhan, Preeti and Mishra, Saurabh and Siddaramappa, Shivakumara and Pradeep, Bulagonda Eswarappa and Singh, Amit and Chakrapani, Harinath (2017) ``On demand'' redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor. In: CHEMICAL SCIENCE, 8 (7). pp. 4967-4972.

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Abstract

Understanding the mechanisms of antimicrobial resistance (AMR) will help launch a counter-offensive against human pathogens that threaten our ability to effectively treat common infections. Herein, we report bis(4-nitrobenzyl)sulfanes, which are activated by a bacterial enzyme to produce hydrogen sulfide (H2S) gas. We found that H2S helps maintain redox homeostasis and protects bacteria against antibiotic-triggered oxidative stress ``on demand'', through activation of alternate respiratory oxidases and cellular antioxidants. We discovered, a hitherto unknown role for this gas, that chemical inhibition of H2S biosynthesis reversed antibiotic resistance in multidrug-resistant (MDR) uropathogenic Escherichia coli strains of clinical origin, whereas exposure to the H2S donor restored drug tolerance. Together, our study provides a greater insight into the dynamic defence mechanisms of this gas, modes of antibiotic action as well as resistance while progressing towards new pharmacological targets to address AMR.

Item Type:	Journal Article
Publication:	CHEMICAL SCIENCE
Additional Information:	Copy right for this article belongs to the ROYAL SOC CHEMISTRY, THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	21 Jul 2017 09:25
Last Modified:	21 Jul 2017 09:25
URI:	http://eprints.iisc.ac.in/id/eprint/57446

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