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:	João S Rebelo, Célia P F Domingues, Francisca Monteiro, Teresa Nogueira, Francisco Dionisio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b23cf8531dac46a3bb32c1f4220b3e19
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spelling	oai:doaj.org-article:b23cf8531dac46a3bb32c1f4220b3e192021-12-02T20:06:21ZBacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities.1932-620310.1371/journal.pone.0246500https://doaj.org/article/b23cf8531dac46a3bb32c1f4220b3e192021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0246500https://doaj.org/toc/1932-6203Antibiotic-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.João S RebeloCélia P F DominguesFrancisca MonteiroTeresa NogueiraFrancisco DionisioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0246500 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q João S Rebelo Célia P F Domingues Francisca Monteiro Teresa Nogueira Francisco Dionisio Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities.
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.
format	article
author	João S Rebelo Célia P F Domingues Francisca Monteiro Teresa Nogueira Francisco Dionisio
author_facet	João S Rebelo Célia P F Domingues Francisca Monteiro Teresa Nogueira Francisco Dionisio
author_sort	João S Rebelo
title	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_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_sort	bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b23cf8531dac46a3bb32c1f4220b3e19
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Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities.

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