Mycobacterium marinum Causes a Latent Infection that Can Be Reactivated by Gamma Irradiation in Adult Zebrafish


Näytä suppeat kuvailutiedot Parikka, Mataleena Hammarén, Milka M Harjula, Sanna-Kaisa Halfpenny, J A Oksanen, Kaisa E Lahtinen, Marika J Pajula, Elina T Pesu, Marko Rämet, Mika 2012-10-19T07:29:10Z 2012-10-19T07:29:10Z 2012
dc.identifier.issn 1553-7366 -
dc.description Public Library of Science open access -
dc.description.abstract The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experimental intraperitoneal infection with a low dose (~35 bacteria) of Mycobacterium marinum, results in the development of a latent disease in most individuals. The infection is characterized by limited mortality (25%), stable bacterial loads 4 weeks following infection and constant numbers of highly organized granulomas in few target organs. The majority of bacteria are dormant during a latent mycobacterial infection in zebrafish, and can be activated by resuscitation promoting factor ex vivo. In 5–10% of tuberculosis cases in humans, the disease is reactivated usually as a consequence of immune suppression. In our model, we are able to show that reactivation can be efficiently induced in infected zebrafish by γ-irradiation that transiently depletes granulo/monocyte and lymphocyte pools, as determined by flow cytometry. This immunosuppression causes reactivation of the dormant mycobacterial population and a rapid outgrowth of bacteria, leading to 88% mortality in four weeks. In this study, the adult zebrafish presents itself as a unique non-mammalian vertebrate model for studying the development of latency, regulation of mycobacterial dormancy, as well as reactivation of latent or subclinical tuberculosis. The possibilities for screening for host and pathogen factors affecting the disease progression, and identifying novel therapeutic agents and vaccine targets make this established model especially attractive. -
dc.language.iso en -
dc.title Mycobacterium marinum Causes a Latent Infection that Can Be Reactivated by Gamma Irradiation in Adult Zebrafish -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal Article| -
dc.identifier.urn URN:NBN:fi:uta-201210191059 -
dc.identifier.doi 10.1371/journal.ppat.1002944 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Lääketieteen bioteknologia | en=Medical biotechnology| -
dc.administrativeunit fi=Biolääketieteellisen teknologian yksikkö | en=Institute of Biomedical Technology| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title Plos Pathogens -
dc.journal.volume 8 -
dc.journal.number 9 -
dc.journal.volumepagerange 1-14 -
dc.journal.url -
dc.ismoreauthorsthanlisted 0 -

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