ESX-5-deficient Mycobacterium marinum is hypervirulent in adult zebrafish

Handle URI:
http://hdl.handle.net/10754/562096
Title:
ESX-5-deficient Mycobacterium marinum is hypervirulent in adult zebrafish
Authors:
Weerdenburg, Eveline M.; Abdallah, Abdallah; Mitra, Suman; De Punder, Karin; Van Der Wel, Nicole N.; Bird, Steve; Appelmelk, Ben J.; Bitter, Wilbert M.; Van Der Sar, Astrid M.
Abstract:
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 pro-inflammatory 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.
KAUST Department:
Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division
Publisher:
Wiley-Blackwell
Journal:
Cellular Microbiology
Issue Date:
15-Feb-2012
DOI:
10.1111/j.1462-5822.2012.01755.x
PubMed ID:
22256857
Type:
Article
ISSN:
14625814
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorWeerdenburg, Eveline M.en
dc.contributor.authorAbdallah, Abdallahen
dc.contributor.authorMitra, Sumanen
dc.contributor.authorDe Punder, Karinen
dc.contributor.authorVan Der Wel, Nicole N.en
dc.contributor.authorBird, Steveen
dc.contributor.authorAppelmelk, Ben J.en
dc.contributor.authorBitter, Wilbert M.en
dc.contributor.authorVan Der Sar, Astrid M.en
dc.date.accessioned2015-08-03T09:44:41Zen
dc.date.available2015-08-03T09:44:41Zen
dc.date.issued2012-02-15en
dc.identifier.issn14625814en
dc.identifier.pmid22256857en
dc.identifier.doi10.1111/j.1462-5822.2012.01755.xen
dc.identifier.urihttp://hdl.handle.net/10754/562096en
dc.description.abstractESX-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 pro-inflammatory 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.en
dc.publisherWiley-Blackwellen
dc.titleESX-5-deficient Mycobacterium marinum is hypervirulent in adult zebrafishen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalCellular Microbiologyen
dc.contributor.institutionDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, Netherlandsen
dc.contributor.institutionDivision of Cell Biology-B6, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlandsen
dc.contributor.institutionScottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdomen
kaust.authorAbdallah, Abdallahen

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