Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus

Detalhes bibliográficos
Autor(a) principal: Chung, Marilyn
Data de Publicação: 2018
Outros Autores: Borges, Vitor, Gomes, João Paulo, de Lencastre, Herminia, Tomasz, Alexander
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6278
Resumo: Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029783/
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spelling Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureusAnti-Bacterial AgentsBiofilmsDrug Resistance, BacterialGene Expression Regulation, BacterialGenome, BacterialGenotypeMicrobial Sensitivity TestsOxacillinStaphylococcal InfectionsStaphylococcus aureusWhole Genome SequencingMutationPhenotypeFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029783/Addition of β-lactam antibiotics to growing cultures of bacteria inhibit synthesis of the bacterial cell wall peptidoglycan accompanied by killing (loss of viable titer) and lysis (physical disintegration) of the cells. However, it has also been well established that these antibiotics are not effective in killing non-growing or slow-growing bacteria and the mechanism of this "antibiotic tolerance" is not well understood. In this study, we report on the genetic basis and phenotypic properties of an antibiotic tolerant derivative of the methicillin susceptible S. aureus strain 27s. Cultures were exposed to "pulses" of high concentrations of oxacillin followed by outgrowth of the surviving bacteria. This procedure quickly selected for antibiotic tolerant mutants with an increased ability to survive antibiotic treatment without increase in the MIC value for the antibiotic. Such mutants also exhibited longer lag phase, decreased lysis, virtually no change in antibiotic susceptibilities, cross tolerance to D-cycloserine and vancomycin, and increase in biofilm formation in the presence of high concentrations of oxacillin. Whole genome sequencing showed that these altered properties were linked to mutations in the atl and gdpP genes.This work was financially supported by a US Public Health Service Award 2 R01 AI457838- 15 awarded to AT and by funds from the RB Roberts Bacterial Antibiotic Resistance Group (BARG) and by MOSTMICRO Project (LISBOA-01- 0145-FEDER-007660) funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalizac¸ão (POCI); and by national funds through FCT - Fundac¸ão para a Ciência e a Tecnologia and project ONEIDA (LISBOA-01-0145-FEDER-016417) co-funded by FEEI - "Fundos Europeus Estruturais e de Investimento" from "Programa Operacional Regional Lisboa 2020" and by national funds from FCT.Public Library of ScienceRepositório Científico do Instituto Nacional de SaúdeChung, MarilynBorges, VitorGomes, João Paulode Lencastre, HerminiaTomasz, Alexander2019-03-22T15:44:47Z2018-07-032018-07-03T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6278engPLoS One. 2018 Jul 3;13(7):e0199707. doi: 10.1371/journal.pone.0199707. eCollection 20181932-620310.1371/journal.pone.0199707info: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:RCAAP2023-07-20T15:41:19Zoai:repositorio.insa.pt:10400.18/6278Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:40:56.678587Repositório 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 Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
title Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
spellingShingle Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
Chung, Marilyn
Anti-Bacterial Agents
Biofilms
Drug Resistance, Bacterial
Gene Expression Regulation, Bacterial
Genome, Bacterial
Genotype
Microbial Sensitivity Tests
Oxacillin
Staphylococcal Infections
Staphylococcus aureus
Whole Genome Sequencing
Mutation
Phenotype
title_short Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
title_full Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
title_fullStr Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
title_full_unstemmed Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
title_sort Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureus
author Chung, Marilyn
author_facet Chung, Marilyn
Borges, Vitor
Gomes, João Paulo
de Lencastre, Herminia
Tomasz, Alexander
author_role author
author2 Borges, Vitor
Gomes, João Paulo
de Lencastre, Herminia
Tomasz, Alexander
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Chung, Marilyn
Borges, Vitor
Gomes, João Paulo
de Lencastre, Herminia
Tomasz, Alexander
dc.subject.por.fl_str_mv Anti-Bacterial Agents
Biofilms
Drug Resistance, Bacterial
Gene Expression Regulation, Bacterial
Genome, Bacterial
Genotype
Microbial Sensitivity Tests
Oxacillin
Staphylococcal Infections
Staphylococcus aureus
Whole Genome Sequencing
Mutation
Phenotype
topic Anti-Bacterial Agents
Biofilms
Drug Resistance, Bacterial
Gene Expression Regulation, Bacterial
Genome, Bacterial
Genotype
Microbial Sensitivity Tests
Oxacillin
Staphylococcal Infections
Staphylococcus aureus
Whole Genome Sequencing
Mutation
Phenotype
description Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029783/
publishDate 2018
dc.date.none.fl_str_mv 2018-07-03
2018-07-03T00:00:00Z
2019-03-22T15:44:47Z
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/10400.18/6278
url http://hdl.handle.net/10400.18/6278
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS One. 2018 Jul 3;13(7):e0199707. doi: 10.1371/journal.pone.0199707. eCollection 2018
1932-6203
10.1371/journal.pone.0199707
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 Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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