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Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities

Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacteria detoxify the medium through antibiotic degradation or modification, a phenomenon denominated as indirect resistance. However, it is unclear how susceptible cells survive while the medium is still tox...

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Autores principales: Rebelo, João S., Domingues, Célia P. F., Monteiro, Francisca, Nogueira, Teresa, Dionisio, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412311/
https://www.ncbi.nlm.nih.gov/pubmed/34473689
http://dx.doi.org/10.1371/journal.pone.0246500
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author Rebelo, João S.
Domingues, Célia P. F.
Monteiro, Francisca
Nogueira, Teresa
Dionisio, Francisco
author_facet Rebelo, João S.
Domingues, Célia P. F.
Monteiro, Francisca
Nogueira, Teresa
Dionisio, Francisco
author_sort Rebelo, João S.
collection PubMed
description Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacteria detoxify the medium through antibiotic degradation or modification, a phenomenon denominated as indirect resistance. However, it is unclear how susceptible cells survive while the medium is still toxic. One explanation relies on the speed of detoxification, and another, non-exclusive explanation, relies on persistence, a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance to understand whether persistence is necessary to explain the survival of susceptible cells. Depending on the strain and experimental conditions, the decay of persister populations may follow an exponential or a power-law distribution. Therefore, we studied the impact of both distributions in the simulations. Moreover, we studied the impact of considering that persister cells have a mechanism to sense the presence of a toxic substance–a mechanism that would enable cells to leave the dormant state when the medium becomes nontoxic. The simulations show that surviving susceptible cells under indirect resistance may originate both from persister and non-persister populations if the density of detoxifying cells is high. However, persistence was necessary when the initial density of detoxifying cells was low, although persister cells remained in that dormancy state for just a few hours. Finally, the results of our simulations are consistent both with exponential and power-law decay of the persistence population. Whether indirect resistance involves persistence should impact antibiotic treatments.
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spelling pubmed-84123112021-09-03 Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities Rebelo, João S. Domingues, Célia P. F. Monteiro, Francisca Nogueira, Teresa Dionisio, Francisco PLoS One Research Article Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacteria detoxify the medium through antibiotic degradation or modification, a phenomenon denominated as indirect resistance. However, it is unclear how susceptible cells survive while the medium is still toxic. One explanation relies on the speed of detoxification, and another, non-exclusive explanation, relies on persistence, a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance to understand whether persistence is necessary to explain the survival of susceptible cells. Depending on the strain and experimental conditions, the decay of persister populations may follow an exponential or a power-law distribution. Therefore, we studied the impact of both distributions in the simulations. Moreover, we studied the impact of considering that persister cells have a mechanism to sense the presence of a toxic substance–a mechanism that would enable cells to leave the dormant state when the medium becomes nontoxic. The simulations show that surviving susceptible cells under indirect resistance may originate both from persister and non-persister populations if the density of detoxifying cells is high. However, persistence was necessary when the initial density of detoxifying cells was low, although persister cells remained in that dormancy state for just a few hours. Finally, the results of our simulations are consistent both with exponential and power-law decay of the persistence population. Whether indirect resistance involves persistence should impact antibiotic treatments. Public Library of Science 2021-09-02 /pmc/articles/PMC8412311/ /pubmed/34473689 http://dx.doi.org/10.1371/journal.pone.0246500 Text en © 2021 Rebelo et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rebelo, João S.
Domingues, Célia P. F.
Monteiro, Francisca
Nogueira, Teresa
Dionisio, Francisco
Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities
title Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities
title_full Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities
title_fullStr Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities
title_full_unstemmed Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities
title_short Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities
title_sort bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412311/
https://www.ncbi.nlm.nih.gov/pubmed/34473689
http://dx.doi.org/10.1371/journal.pone.0246500
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