The power of dying slowly - persistence as unintentional dormancy

Detalhes bibliográficos
Autor(a) principal: Rebelo, João S.
Data de Publicação: 2021
Outros Autores: Domingues, Célia P. F., Monteiro, Francisca, Nogueira, Teresa, Dionisio, Francisco
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/47528
Resumo: Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of −2. Studying persisters’ decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to −2, which is the expected value if persistence results from unintentional errors. Whether persisters are cells in a moribund state or, on the contrary, result from a genetic program, should impact the research of anti-persistent drugs.
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spelling The power of dying slowly - persistence as unintentional dormancyPersistence; power-law; exponential decay; indirect resistance; indirect pathogenicity; antibiotic resistance; beta-lactamase; beta-lactais; ampicillinPersistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of −2. Studying persisters’ decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to −2, which is the expected value if persistence results from unintentional errors. Whether persisters are cells in a moribund state or, on the contrary, result from a genetic program, should impact the research of anti-persistent drugs.BioRxivRepositório da Universidade de LisboaRebelo, João S.Domingues, Célia P. F.Monteiro, FranciscaNogueira, TeresaDionisio, Francisco2021-04-22T19:27:43Z2021-01-202021-01-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47528eng10.1101/2021.01.20.427471info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:50:30Zoai:repositorio.ul.pt:10451/47528Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:59:32.886484Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The power of dying slowly - persistence as unintentional dormancy
title The power of dying slowly - persistence as unintentional dormancy
spellingShingle The power of dying slowly - persistence as unintentional dormancy
Rebelo, João S.
Persistence; power-law; exponential decay; indirect resistance; indirect pathogenicity; antibiotic resistance; beta-lactamase; beta-lactais; ampicillin
title_short The power of dying slowly - persistence as unintentional dormancy
title_full The power of dying slowly - persistence as unintentional dormancy
title_fullStr The power of dying slowly - persistence as unintentional dormancy
title_full_unstemmed The power of dying slowly - persistence as unintentional dormancy
title_sort The power of dying slowly - persistence as unintentional dormancy
author Rebelo, João S.
author_facet Rebelo, João S.
Domingues, Célia P. F.
Monteiro, Francisca
Nogueira, Teresa
Dionisio, Francisco
author_role author
author2 Domingues, Célia P. F.
Monteiro, Francisca
Nogueira, Teresa
Dionisio, Francisco
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Rebelo, João S.
Domingues, Célia P. F.
Monteiro, Francisca
Nogueira, Teresa
Dionisio, Francisco
dc.subject.por.fl_str_mv Persistence; power-law; exponential decay; indirect resistance; indirect pathogenicity; antibiotic resistance; beta-lactamase; beta-lactais; ampicillin
topic Persistence; power-law; exponential decay; indirect resistance; indirect pathogenicity; antibiotic resistance; beta-lactamase; beta-lactais; ampicillin
description Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of −2. Studying persisters’ decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to −2, which is the expected value if persistence results from unintentional errors. Whether persisters are cells in a moribund state or, on the contrary, result from a genetic program, should impact the research of anti-persistent drugs.
publishDate 2021
dc.date.none.fl_str_mv 2021-04-22T19:27:43Z
2021-01-20
2021-01-20T00:00:00Z
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