Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages

Detalhes bibliográficos
Autor(a) principal: Sousa, Sara
Data de Publicação: 2019
Outros Autores: Borges, Vítor, João, Inês, Gomes, João Paulo, Jordão, Luisa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6411
Resumo: Nontuberculous Mycobacteria (NTM) respiratory infections have been gradually increasing. Here, THP-1 cells were used as a model to evaluate intracellular persistence of three NTM species (reference and clinical strains) in human alveolar macrophages. The contribution of phagosome acidification, nitric oxide (NO) production and cell dead on NTM intracellular fate was assessed. In addition, strains were characterized regarding their repertoire of virulence factors by whole-genome sequencing. NTM experienced different intracellular fates: M. smegmatis and M. fortuitum ATCC 6841 were cleared within 24h. In contrast, M. avium strains (reference/clinical) and M. fortuitum clinical strain were able to replicate. Despite this fact, unexpectedly high percentages of acidified phagosomes were found harbouring rab7, but not CD63. All NTM were able to survive in vitro at acidic pHs, with the exception of M. smegmatis. Our data further suggested a minor role for NO in intracellular persistence and that apoptosis mediated by caspase 8 and 3/7, but not necrosis, is triggered during NTM infection. Insights regarding the bacteria genomic backbone corroborated the virulence potential of M. avium and M. fortuitum. In conclusion, the phenotypic traits detected contrast with those described for M. tuberculosis, pointing out that NTM adopt distinct strategies to manipulate the host immune defense and persist intracellularly.
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spelling Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar MacrophagesNontuberculous MycobacteriaHost-pathogen InteractionMacrophagespHVirulenceNTM InfectionRespiratory InfectionsInfecções RespiratóriasAgentes Microbianos e AmbienteNontuberculous Mycobacteria (NTM) respiratory infections have been gradually increasing. Here, THP-1 cells were used as a model to evaluate intracellular persistence of three NTM species (reference and clinical strains) in human alveolar macrophages. The contribution of phagosome acidification, nitric oxide (NO) production and cell dead on NTM intracellular fate was assessed. In addition, strains were characterized regarding their repertoire of virulence factors by whole-genome sequencing. NTM experienced different intracellular fates: M. smegmatis and M. fortuitum ATCC 6841 were cleared within 24h. In contrast, M. avium strains (reference/clinical) and M. fortuitum clinical strain were able to replicate. Despite this fact, unexpectedly high percentages of acidified phagosomes were found harbouring rab7, but not CD63. All NTM were able to survive in vitro at acidic pHs, with the exception of M. smegmatis. Our data further suggested a minor role for NO in intracellular persistence and that apoptosis mediated by caspase 8 and 3/7, but not necrosis, is triggered during NTM infection. Insights regarding the bacteria genomic backbone corroborated the virulence potential of M. avium and M. fortuitum. In conclusion, the phenotypic traits detected contrast with those described for M. tuberculosis, pointing out that NTM adopt distinct strategies to manipulate the host immune defense and persist intracellularly.MDPIRepositório Científico do Instituto Nacional de SaúdeSousa, SaraBorges, VítorJoão, InêsGomes, João PauloJordão, Luisa2019-05-30T09:43:12Z2019-04-262019-04-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6411engMicroorganisms. 2019 Apr 26;7(5). pii: E113. doi: 10.3390/microorganisms70501132076-260710.3390/microorganisms7050113info: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:RCAAP2023-07-20T15:41:24Zoai:repositorio.insa.pt:10400.18/6411Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:04.247362Repositório 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 Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
title Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
spellingShingle Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
Sousa, Sara
Nontuberculous Mycobacteria
Host-pathogen Interaction
Macrophages
pH
Virulence
NTM Infection
Respiratory Infections
Infecções Respiratórias
Agentes Microbianos e Ambiente
title_short Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
title_full Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
title_fullStr Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
title_full_unstemmed Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
title_sort Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
author Sousa, Sara
author_facet Sousa, Sara
Borges, Vítor
João, Inês
Gomes, João Paulo
Jordão, Luisa
author_role author
author2 Borges, Vítor
João, Inês
Gomes, João Paulo
Jordão, Luisa
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 Sousa, Sara
Borges, Vítor
João, Inês
Gomes, João Paulo
Jordão, Luisa
dc.subject.por.fl_str_mv Nontuberculous Mycobacteria
Host-pathogen Interaction
Macrophages
pH
Virulence
NTM Infection
Respiratory Infections
Infecções Respiratórias
Agentes Microbianos e Ambiente
topic Nontuberculous Mycobacteria
Host-pathogen Interaction
Macrophages
pH
Virulence
NTM Infection
Respiratory Infections
Infecções Respiratórias
Agentes Microbianos e Ambiente
description Nontuberculous Mycobacteria (NTM) respiratory infections have been gradually increasing. Here, THP-1 cells were used as a model to evaluate intracellular persistence of three NTM species (reference and clinical strains) in human alveolar macrophages. The contribution of phagosome acidification, nitric oxide (NO) production and cell dead on NTM intracellular fate was assessed. In addition, strains were characterized regarding their repertoire of virulence factors by whole-genome sequencing. NTM experienced different intracellular fates: M. smegmatis and M. fortuitum ATCC 6841 were cleared within 24h. In contrast, M. avium strains (reference/clinical) and M. fortuitum clinical strain were able to replicate. Despite this fact, unexpectedly high percentages of acidified phagosomes were found harbouring rab7, but not CD63. All NTM were able to survive in vitro at acidic pHs, with the exception of M. smegmatis. Our data further suggested a minor role for NO in intracellular persistence and that apoptosis mediated by caspase 8 and 3/7, but not necrosis, is triggered during NTM infection. Insights regarding the bacteria genomic backbone corroborated the virulence potential of M. avium and M. fortuitum. In conclusion, the phenotypic traits detected contrast with those described for M. tuberculosis, pointing out that NTM adopt distinct strategies to manipulate the host immune defense and persist intracellularly.
publishDate 2019
dc.date.none.fl_str_mv 2019-05-30T09:43:12Z
2019-04-26
2019-04-26T00:00:00Z
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/10400.18/6411
url http://hdl.handle.net/10400.18/6411
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Microorganisms. 2019 Apr 26;7(5). pii: E113. doi: 10.3390/microorganisms7050113
2076-2607
10.3390/microorganisms7050113
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 MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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