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ESX-5-deficient Mycobacterium marinum is hypervirulent in adult zebrafish.
MedLine Citation:
PMID:  22256857     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ESX-5 is a mycobacterial type VII protein secretion system responsible for transport of numerous PE and PPE proteins. It is involved in the induction of host cell death and modulation of the cytokine response in vitro. In this work, we studied the effects of ESX-5 in embryonic and adult zebrafish using Mycobacterium marinum. We found that ESX-5-deficient M. marinum was slightly attenuated in zebrafish embryos. Surprisingly, the same mutant showed highly increased virulence in adult zebrafish, characterized by increased bacterial loads and early onset of granuloma formation with rapid development of necrotic centres. This early onset of granuloma formation was accompanied by an increased expression of proinflammatory cytokines and tissue remodelling genes in zebrafish infected with the ESX-5 mutant. Experiments using RAG-1-deficient zebrafish showed that the increased virulence of the ESX-5 mutant was not dependent on the adaptive immune system. Mixed infection experiments with wild-type and ESX-5 mutant bacteria showed that the latter had a specific advantage in adult zebrafish and outcompeted wild-type bacteria. Together our experiments indicate that ESX-5- mediated protein secretion is used by M. marinum to establish a moderate and persistent infection. © 2012 Blackwell Publishing Ltd.
Authors:
Eveline M Weerdenburg; Abdallah M Abdallah; Suman Mitra; Karin de Punder; Nicole N van der Wel; Steve Bird; Ben J Appelmelk; Wilbert Bitter; Astrid M van der Sar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-18
Journal Detail:
Title:  Cellular microbiology     Volume:  -     ISSN:  1462-5822     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands, Division of Cell Biology-B6, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands, Scottish Fish Immonology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen, UK.
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