"On demand" redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor. Issue 7 (16th May 2017)

• Record Type: Journal Article
• Authors: Shukla, Prashant; Khodade, Vinayak S.; SharathChandra, Mallojjala; Chauhan, Preeti; Mishra, Saurabh; Siddaramappa, Shivakumara; Pradeep, Bulagonda Eswarappa; Singh, Amit; Chakrapani, Harinath
• Is Part Of: Chemical science. Volume 8:Issue 7(2017)
• Page Start: 4967
• Page End: 4972
• Publication Date: 2017-05-16
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7sc00873b
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Enhancement of hydrogen sulfide in bacteria reveals a key role for this gas in mediating antibiotic resistance. 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 (H2 S) gas. We found that H2 S 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 H2 S biosynthesis reversed antibiotic resistance in multidrug-resistant (MDR) uropathogenic Escherichia coli strains of clinical origin, whereas exposure to the H2 S 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.