학술논문
"On demand" redox buffering by H 2 S contributes to antibiotic resistance revealed by a bacteria-specific H 2 S donor.
Document Type
Academic Journal
Author
Shukla P; Department of Microbiology and Cell Biology , Centre for Infectious Disease and Research , Indian Institute of Science , Bangalore 5600012 , Karnataka , India . Email: asingh@mcbl.iisc.ernet.in.; International Centre for Genetic Engineering and Biotechnology , New Delhi , India.; Khodade VS; Department of Chemistry , Indian Institute of Science Education and Research Pune , Dr Homi Bhabha Road, Pashan , Pune 411 008 , Maharashtra , India . Email: harinath@iiserpune.ac.in.; SharathChandra M; Department of Chemistry , Indian Institute of Science Education and Research Pune , Dr Homi Bhabha Road, Pashan , Pune 411 008 , Maharashtra , India . Email: harinath@iiserpune.ac.in.; Chauhan P; Department of Chemistry , Indian Institute of Science Education and Research Pune , Dr Homi Bhabha Road, Pashan , Pune 411 008 , Maharashtra , India . Email: harinath@iiserpune.ac.in.; Mishra S; Department of Microbiology and Cell Biology , Centre for Infectious Disease and Research , Indian Institute of Science , Bangalore 5600012 , Karnataka , India . Email: asingh@mcbl.iisc.ernet.in.; Siddaramappa S; Institute of Bioinformatics and Applied Biotechnology , Bengaluru 5600100 , Karnataka , India.; Pradeep BE; Sri Sathya Sai Institute of Higher Learning , Vidyagiri , Prasanthi Nilayam , Andhra Pradesh , India.; Singh A; Department of Microbiology and Cell Biology , Centre for Infectious Disease and Research , Indian Institute of Science , Bangalore 5600012 , Karnataka , India . Email: asingh@mcbl.iisc.ernet.in.; Chakrapani H; Department of Chemistry , Indian Institute of Science Education and Research Pune , Dr Homi Bhabha Road, Pashan , Pune 411 008 , Maharashtra , India . Email: harinath@iiserpune.ac.in.
Source
Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101545951 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2041-6520 (Print) Linking ISSN: 20416520 NLM ISO Abbreviation: Chem Sci Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2041-6520
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 (H 2 S) gas. We found that H 2 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 H 2 S biosynthesis reversed antibiotic resistance in multidrug-resistant (MDR) uropathogenic Escherichia coli strains of clinical origin, whereas exposure to the H 2 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.