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MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters

BACKGROUND: Persistence is a natural phenomenon whereby a subset of a population of isogenic bacteria either grow slow or become dormant conferring them with the ability to withstand various stresses including antibiotics. In a clinical setting bacterial persistence often leads to the recalcitrance...

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Autores principales: Alexander, Cyrus, Guru, Ankeeta, Pradhan, Pinkilata, Mallick, Sunanda, Mahanandia, Nimai Charan, Subudhi, Bharat Bhusan, Beuria, Tushar Kant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590665/
https://www.ncbi.nlm.nih.gov/pubmed/33109090
http://dx.doi.org/10.1186/s12860-020-00316-8
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author Alexander, Cyrus
Guru, Ankeeta
Pradhan, Pinkilata
Mallick, Sunanda
Mahanandia, Nimai Charan
Subudhi, Bharat Bhusan
Beuria, Tushar Kant
author_facet Alexander, Cyrus
Guru, Ankeeta
Pradhan, Pinkilata
Mallick, Sunanda
Mahanandia, Nimai Charan
Subudhi, Bharat Bhusan
Beuria, Tushar Kant
author_sort Alexander, Cyrus
collection PubMed
description BACKGROUND: Persistence is a natural phenomenon whereby a subset of a population of isogenic bacteria either grow slow or become dormant conferring them with the ability to withstand various stresses including antibiotics. In a clinical setting bacterial persistence often leads to the recalcitrance of various infections increasing the treatment time and cost. Additionally, some studies also indicate that persistence can also pave way for the emergence of resistant strains. In a laboratory setting this persistent phenotype is enriched in nutritionally deprived environments. Consequently, in a batch culture the late stationary phase is enriched with persistent bacteria. The mechanism of persister cell formation and its regulation is not well understood. Toxin-antitoxin (TA) systems have been implicated to be responsible for bacterial persistence and rifampicin is used to treat highly persistent bacterial strains. The current study tries to explore a possible interaction between rifampicin and the MazEF TA system that furthers the former’s success rate in treating persistent bacteria. RESULTS: In the current study we found that the population of bacteria in the death phase of a batch culture consists of metabolically inactive live cells resembling persisters, which showed higher membrane depolarization as compared to the log phase bacteria. We also observed an increase in the expression of the MazEF TA modules in this phase. Since rifampicin is used to kill the persisters, we assessed the interaction of rifampicin with MazEF complex. We showed that rifampicin moderately interacts with MazEF complex with 1:1 stoichiometry. CONCLUSION: Our study suggests that the interaction of rifampicin with MazEF complex might play an important role in inhibition of persisters. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-020-00316-8.
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spelling pubmed-75906652020-10-27 MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters Alexander, Cyrus Guru, Ankeeta Pradhan, Pinkilata Mallick, Sunanda Mahanandia, Nimai Charan Subudhi, Bharat Bhusan Beuria, Tushar Kant BMC Mol Cell Biol Research Article BACKGROUND: Persistence is a natural phenomenon whereby a subset of a population of isogenic bacteria either grow slow or become dormant conferring them with the ability to withstand various stresses including antibiotics. In a clinical setting bacterial persistence often leads to the recalcitrance of various infections increasing the treatment time and cost. Additionally, some studies also indicate that persistence can also pave way for the emergence of resistant strains. In a laboratory setting this persistent phenotype is enriched in nutritionally deprived environments. Consequently, in a batch culture the late stationary phase is enriched with persistent bacteria. The mechanism of persister cell formation and its regulation is not well understood. Toxin-antitoxin (TA) systems have been implicated to be responsible for bacterial persistence and rifampicin is used to treat highly persistent bacterial strains. The current study tries to explore a possible interaction between rifampicin and the MazEF TA system that furthers the former’s success rate in treating persistent bacteria. RESULTS: In the current study we found that the population of bacteria in the death phase of a batch culture consists of metabolically inactive live cells resembling persisters, which showed higher membrane depolarization as compared to the log phase bacteria. We also observed an increase in the expression of the MazEF TA modules in this phase. Since rifampicin is used to kill the persisters, we assessed the interaction of rifampicin with MazEF complex. We showed that rifampicin moderately interacts with MazEF complex with 1:1 stoichiometry. CONCLUSION: Our study suggests that the interaction of rifampicin with MazEF complex might play an important role in inhibition of persisters. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-020-00316-8. BioMed Central 2020-10-27 /pmc/articles/PMC7590665/ /pubmed/33109090 http://dx.doi.org/10.1186/s12860-020-00316-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Alexander, Cyrus
Guru, Ankeeta
Pradhan, Pinkilata
Mallick, Sunanda
Mahanandia, Nimai Charan
Subudhi, Bharat Bhusan
Beuria, Tushar Kant
MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
title MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
title_full MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
title_fullStr MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
title_full_unstemmed MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
title_short MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
title_sort mazef-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590665/
https://www.ncbi.nlm.nih.gov/pubmed/33109090
http://dx.doi.org/10.1186/s12860-020-00316-8
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