Publicação
Evidence for an intramacrophage growth phase of Mycobacterium ulcerans
| 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. |
|---|---|
| Autores principais: | Torrado, Egídio |
| Outros Autores: | Fraga, Alexandra Gabriel; Castro, António G.; Stragier, Pieter; Meyers, Wayne M.; Portaels, Françoise; Silva, Manuel T.; Pedrosa, Jorge |
| Assunto: | 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 |
| Ano: | 2007 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866876709783994368 |
|---|---|
| author | Torrado, Egídio |
| 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 |
| 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 |
| contributor_name_str_mv | Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Torrado, Egídio\"},{\"Person.name\":\"Fraga, Alexandra Gabriel\"},{\"Person.name\":\"Castro, António G.\"},{\"Person.name\":\"Stragier, Pieter\"},{\"Person.name\":\"Meyers, Wayne M.\"},{\"Person.name\":\"Portaels, Françoise\"},{\"Person.name\":\"Silva, Manuel T.\"},{\"Person.name\":\"Pedrosa, Jorge\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Torrado, Egídio Fraga, Alexandra Gabriel Castro, António G. Stragier, Pieter Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Pedrosa, Jorge |
| datacite.date.Accepted.fl_str_mv | 2007-02-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2020-10-27T13:25:46Z |
| datacite.date.embargoed.fl_str_mv | 2020-10-27T13:25:46Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.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 |
| datacite.titles.title.fl_str_mv | Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
| dc.contributor.none.fl_str_mv | Universidade do Minho |
| dc.creator.none.fl_str_mv | Torrado, Egídio Fraga, Alexandra Gabriel Castro, António G. Stragier, Pieter Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Pedrosa, Jorge |
| dc.date.Accepted.fl_str_mv | 2007-02-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2020-10-27T13:25:46Z |
| dc.date.embargoed.fl_str_mv | 2020-10-27T13:25:46Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/67769 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | American Society for Microbiology (ASM) |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.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 |
| dc.title.fl_str_mv | Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://prod-dspace.uminho.pt/bitstreams/a2a239e7-64ff-4186-90c3-df867fbc1361/download |
| id | rum_ebfc084ab9f25bbb0a43c64ea686b7bc |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/67769 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/67769 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Torrado, Egídio Fraga, Alexandra Gabriel Castro, António G. Stragier, Pieter Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Pedrosa, Jorge |
| publishDate | 2007 |
| publisher.none.fl_str_mv | American Society for Microbiology (ASM) |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engAmerican Society for Microbiology (ASM)porMycobacterium 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.application/pdfporEvidence for an intramacrophage growth phase of Mycobacterium ulceransTorrado, EgídioFraga, Alexandra GabrielCastro, António G.Stragier, PieterMeyers, Wayne M.Portaels, FrançoiseSilva, Manuel T.Pedrosa, JorgeHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf0019-9567DOIIsPartOf10.1128/IAI.00889-062020-10-27T13:25:46Z2007-022007-02-01T00:00:00ZHandlehttps://hdl.handle.net/1822/67769http://purl.org/coar/access_right/c_abf2open accessAnimalsBacterial ToxinsCells, CulturedDisease Models, AnimalFemaleFootHistocytochemistryHumansMacrolidesMacrophagesMiceMice, Inbred BALB CMicroscopy, Electron, TransmissionMycobacterium Infections, NontuberculousMycobacterium ulceransPhagocytosisSkin Diseases, BacterialSkin Ulcer1099489 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/a2a239e7-64ff-4186-90c3-df867fbc1361/download |
| 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 |
| status | SINGLETON |
| subject.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 |
| title | 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_short | Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
| title_sort | Evidence for an intramacrophage growth phase of Mycobacterium ulcerans |
| 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 |
| topic_facet | 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 |
| url | https://hdl.handle.net/1822/67769 |
| visible | 1 |