Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics

The production of endogenous hydrogen sulfide (H2S) has been shown to confer antibiotic tolerance in all bacteria studied to date. Therefore, this mediator has been speculated to be a universal defense mechanism against antibiotics in bacteria. This is assuming that all bacteria produce endogenous H...

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Main Authors: Ng, Say Yong, Ong, Kai Xun, Surendran, Smitha Thamarath, Sinha, Ameya, Lai, Joey Jia Hui, Chen, Jacqueline, Liang, Jiaqi, Tay, Leona Kwan Sing, Cui, Liang, Loo, Hooi Linn, Ho, Peiying, Han, Jongyoon, Moreira, Wilfried
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/145258
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1452582023-02-28T17:08:33Z Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics Ng, Say Yong Ong, Kai Xun Surendran, Smitha Thamarath Sinha, Ameya Lai, Joey Jia Hui Chen, Jacqueline Liang, Jiaqi Tay, Leona Kwan Sing Cui, Liang Loo, Hooi Linn Ho, Peiying Han, Jongyoon Moreira, Wilfried School of Biological Sciences Science::Biological sciences Hydrogen Sulfide Antibiotic Resistance The production of endogenous hydrogen sulfide (H2S) has been shown to confer antibiotic tolerance in all bacteria studied to date. Therefore, this mediator has been speculated to be a universal defense mechanism against antibiotics in bacteria. This is assuming that all bacteria produce endogenous H2S. In this study, we established that the pathogenic bacteria Acinetobacter baumannii does not produce endogenous H2S, giving us the opportunity to test the effect of exogenous H2S on antibiotic tolerance in a bacterium that does not produce it. By using a H2S-releasing compound to modulate the sulfide content in A. baumannii, we demonstrated that instead of conferring antibiotic tolerance, exogenous H2S sensitized A. baumannii to multiple antibiotic classes, and was able to revert acquired resistance to gentamicin. Exogenous H2S triggered a perturbation of redox and energy homeostasis that translated into hypersensitivity to antibiotic killing. We propose that H2S could be used as an antibiotic-potentiator and resistance-reversion agent in bacteria that do not produce it. Ministry of Health (MOH) National Medical Research Council (NMRC) Singapore-MIT Alliance for Research and Technology (SMART) Published version This work was funded by the National Medical Research Council, Ministry of Health, Singapore under the grant NMRC-OFYIRG-036-2017, and the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (AMR IRG), Singapore-MIT Alliance for Research and Technology (SMART) Centre, Singapore. AS received support from the Singapore—MIT Alliance (SMA) Graduate Fellowship. 2020-12-16T03:08:28Z 2020-12-16T03:08:28Z 2020 Journal Article Ng, S. Y., Ong, K. X., Surendran, S. T., Sinha, A., Lai, J. J. H., Chen, J., . . . Moreira, W. (2020). Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics. Frontiers in Microbiology, 11, 1875-. doi:10.3389/fmicb.2020.01875 1664-302X https://hdl.handle.net/10356/145258 10.3389/fmicb.2020.01875 32849459 11 en NMRC-OFYIRG-036-2017 Frontiers in Microbiology © 2020 Ng, Ong, Surendran, Sinha, Lai, Chen, Liang, Tay, Cui, Loo, Ho, Han and Moreira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Hydrogen Sulfide
Antibiotic Resistance
spellingShingle Science::Biological sciences
Hydrogen Sulfide
Antibiotic Resistance
Ng, Say Yong
Ong, Kai Xun
Surendran, Smitha Thamarath
Sinha, Ameya
Lai, Joey Jia Hui
Chen, Jacqueline
Liang, Jiaqi
Tay, Leona Kwan Sing
Cui, Liang
Loo, Hooi Linn
Ho, Peiying
Han, Jongyoon
Moreira, Wilfried
Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics
description The production of endogenous hydrogen sulfide (H2S) has been shown to confer antibiotic tolerance in all bacteria studied to date. Therefore, this mediator has been speculated to be a universal defense mechanism against antibiotics in bacteria. This is assuming that all bacteria produce endogenous H2S. In this study, we established that the pathogenic bacteria Acinetobacter baumannii does not produce endogenous H2S, giving us the opportunity to test the effect of exogenous H2S on antibiotic tolerance in a bacterium that does not produce it. By using a H2S-releasing compound to modulate the sulfide content in A. baumannii, we demonstrated that instead of conferring antibiotic tolerance, exogenous H2S sensitized A. baumannii to multiple antibiotic classes, and was able to revert acquired resistance to gentamicin. Exogenous H2S triggered a perturbation of redox and energy homeostasis that translated into hypersensitivity to antibiotic killing. We propose that H2S could be used as an antibiotic-potentiator and resistance-reversion agent in bacteria that do not produce it.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Ng, Say Yong
Ong, Kai Xun
Surendran, Smitha Thamarath
Sinha, Ameya
Lai, Joey Jia Hui
Chen, Jacqueline
Liang, Jiaqi
Tay, Leona Kwan Sing
Cui, Liang
Loo, Hooi Linn
Ho, Peiying
Han, Jongyoon
Moreira, Wilfried
format Article
author Ng, Say Yong
Ong, Kai Xun
Surendran, Smitha Thamarath
Sinha, Ameya
Lai, Joey Jia Hui
Chen, Jacqueline
Liang, Jiaqi
Tay, Leona Kwan Sing
Cui, Liang
Loo, Hooi Linn
Ho, Peiying
Han, Jongyoon
Moreira, Wilfried
author_sort Ng, Say Yong
title Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics
title_short Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics
title_full Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics
title_fullStr Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics
title_full_unstemmed Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics
title_sort hydrogen sulfide sensitizes acinetobacter baumannii to killing by antibiotics
publishDate 2020
url https://hdl.handle.net/10356/145258
_version_ 1759853892655382528