The power of dying slowly - persistence as unintentional dormancy
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , |
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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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 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/47528 |
url |
http://hdl.handle.net/10451/47528 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1101/2021.01.20.427471 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
BioRxiv |
publisher.none.fl_str_mv |
BioRxiv |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134541904871424 |