Evidence for an intramacrophage growth phase of Mycobacterium ulcerans
Autor(a) principal: | |
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Data de Publicação: | 2007 |
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/1822/67769 |
Resumo: | Mycobacterium ulcerans is the etiologic agent of Buruli ulcer (BU), an emerging tropical skin disease. Virulent M. ulcerans secretes mycolactone, a cytotoxic exotoxin with a key pathogenic role. M. ulcerans in biopsy specimens has been described as an extracellular bacillus. In vitro assays have suggested a mycolactone-induced inhibition of M. ulcerans uptake by macrophages in which its proliferation has not been demonstrated. Therefore, and uniquely for a mycobacterium, M. ulcerans has been classified as an extracellular pathogen. In specimens from patients and in mouse footpad lesions, extracellular bacilli were concentrated in central necrotic acellular areas; however, we found bacilli within macrophages in surrounding inflammatory infiltrates. We demonstrated that mycolactone-producing M. ulcerans isolates are efficiently phagocytosed by murine macrophages, indicating that the extracellular location of M. ulcerans is not a result of inhibition of phagocytosis. Additionally, we found that M. ulcerans multiplies inside cultured mouse macrophages when low multiplicities of infection are used to prevent early mycolactone-associated cytotoxicity. Following the proliferation phase within macrophages, M. ulcerans induces the lysis of the infected host cells, becoming extracellular. Our data show that M. ulcerans, like M. tuberculosis, is an intracellular parasite with phases of intramacrophage and extracellular multiplication. The occurrence of an intramacrophage phase is in accordance with the development of cell-mediated and delayed-type hypersensitivity responses in BU patients. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Evidence for an intramacrophage growth phase of Mycobacterium ulceransAnimalsBacterial ToxinsCells, CulturedDisease Models, AnimalFemaleFootHistocytochemistryHumansMacrolidesMacrophagesMiceMice, Inbred BALB CMicroscopy, Electron, TransmissionMycobacterium Infections, NontuberculousMycobacterium ulceransPhagocytosisSkin Diseases, BacterialSkin UlcerScience & TechnologyMycobacterium ulcerans is the etiologic agent of Buruli ulcer (BU), an emerging tropical skin disease. Virulent M. ulcerans secretes mycolactone, a cytotoxic exotoxin with a key pathogenic role. M. ulcerans in biopsy specimens has been described as an extracellular bacillus. In vitro assays have suggested a mycolactone-induced inhibition of M. ulcerans uptake by macrophages in which its proliferation has not been demonstrated. Therefore, and uniquely for a mycobacterium, M. ulcerans has been classified as an extracellular pathogen. In specimens from patients and in mouse footpad lesions, extracellular bacilli were concentrated in central necrotic acellular areas; however, we found bacilli within macrophages in surrounding inflammatory infiltrates. We demonstrated that mycolactone-producing M. ulcerans isolates are efficiently phagocytosed by murine macrophages, indicating that the extracellular location of M. ulcerans is not a result of inhibition of phagocytosis. Additionally, we found that M. ulcerans multiplies inside cultured mouse macrophages when low multiplicities of infection are used to prevent early mycolactone-associated cytotoxicity. Following the proliferation phase within macrophages, M. ulcerans induces the lysis of the infected host cells, becoming extracellular. Our data show that M. ulcerans, like M. tuberculosis, is an intracellular parasite with phases of intramacrophage and extracellular multiplication. The occurrence of an intramacrophage phase is in accordance with the development of cell-mediated and delayed-type hypersensitivity responses in BU patients.This work was supported by a grant from the Health Services of Fundação Calouste Gulbenkian and by FCT fellowships Praxis SFRH/ BD/9757/2003 and SFRH/BD/15911/2005 to E. Torrado and A. G. Fraga, respectively.American Society for Microbiology (ASM)Universidade do MinhoTorrado, EgídioFraga, Alexandra GabrielCastro, António G.Stragier, PieterMeyers, Wayne M.Portaels, FrançoiseSilva, Manuel T.Pedrosa, Jorge2007-022007-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/67769eng0019-95671098-552210.1128/IAI.00889-0617145944info: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:RCAAP2023-07-21T12:22:00ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
title |
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
spellingShingle |
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans Torrado, Egídio Animals Bacterial Toxins Cells, Cultured Disease Models, Animal Female Foot Histocytochemistry Humans Macrolides Macrophages Mice Mice, Inbred BALB C Microscopy, Electron, Transmission Mycobacterium Infections, Nontuberculous Mycobacterium ulcerans Phagocytosis Skin Diseases, Bacterial Skin Ulcer Science & Technology |
title_short |
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
title_full |
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
title_fullStr |
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
title_full_unstemmed |
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
title_sort |
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
author |
Torrado, Egídio |
author_facet |
Torrado, Egídio Fraga, Alexandra Gabriel Castro, António G. Stragier, Pieter Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Pedrosa, Jorge |
author_role |
author |
author2 |
Fraga, Alexandra Gabriel Castro, António G. Stragier, Pieter Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Pedrosa, Jorge |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Torrado, Egídio Fraga, Alexandra Gabriel Castro, António G. Stragier, Pieter Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Pedrosa, Jorge |
dc.subject.por.fl_str_mv |
Animals Bacterial Toxins Cells, Cultured Disease Models, Animal Female Foot Histocytochemistry Humans Macrolides Macrophages Mice Mice, Inbred BALB C Microscopy, Electron, Transmission Mycobacterium Infections, Nontuberculous Mycobacterium ulcerans Phagocytosis Skin Diseases, Bacterial Skin Ulcer Science & Technology |
topic |
Animals Bacterial Toxins Cells, Cultured Disease Models, Animal Female Foot Histocytochemistry Humans Macrolides Macrophages Mice Mice, Inbred BALB C Microscopy, Electron, Transmission Mycobacterium Infections, Nontuberculous Mycobacterium ulcerans Phagocytosis Skin Diseases, Bacterial Skin Ulcer Science & Technology |
description |
Mycobacterium ulcerans is the etiologic agent of Buruli ulcer (BU), an emerging tropical skin disease. Virulent M. ulcerans secretes mycolactone, a cytotoxic exotoxin with a key pathogenic role. M. ulcerans in biopsy specimens has been described as an extracellular bacillus. In vitro assays have suggested a mycolactone-induced inhibition of M. ulcerans uptake by macrophages in which its proliferation has not been demonstrated. Therefore, and uniquely for a mycobacterium, M. ulcerans has been classified as an extracellular pathogen. In specimens from patients and in mouse footpad lesions, extracellular bacilli were concentrated in central necrotic acellular areas; however, we found bacilli within macrophages in surrounding inflammatory infiltrates. We demonstrated that mycolactone-producing M. ulcerans isolates are efficiently phagocytosed by murine macrophages, indicating that the extracellular location of M. ulcerans is not a result of inhibition of phagocytosis. Additionally, we found that M. ulcerans multiplies inside cultured mouse macrophages when low multiplicities of infection are used to prevent early mycolactone-associated cytotoxicity. Following the proliferation phase within macrophages, M. ulcerans induces the lysis of the infected host cells, becoming extracellular. Our data show that M. ulcerans, like M. tuberculosis, is an intracellular parasite with phases of intramacrophage and extracellular multiplication. The occurrence of an intramacrophage phase is in accordance with the development of cell-mediated and delayed-type hypersensitivity responses in BU patients. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-02 2007-02-01T00:00:00Z |
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/1822/67769 |
url |
http://hdl.handle.net/1822/67769 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0019-9567 1098-5522 10.1128/IAI.00889-06 17145944 |
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 |
American Society for Microbiology (ASM) |
publisher.none.fl_str_mv |
American Society for Microbiology (ASM) |
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 |
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repository.mail.fl_str_mv |
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1777303740305375232 |