Document Detail

The Type VI secretion system of Burkholderia cenocepacia targets multiple Rho family GTPases disrupting the actin cytoskeleton and the assembly of NADPH oxidase complex in macrophages.
MedLine Citation:
PMID:  22023353     Owner:  NLM     Status:  Publisher    
Burkholderia cenocepacia is a Gram-negative opportunistic pathogen in patients with cystic fibrosis and chronic granulomatous disease. The bacterium survives intracellularly in macrophages within a membrane-bound vacuole (BcCV) that precludes the fusion with lysosomes. The underlying cellular mechanisms and bacterial molecules mediating these phenotypes are unknown. Here, we show that intracellular B. cenocepacia expressing a type VI secretion system (T6SS) targets the activation of the Rac1 and Cdc42 RhoGTPase by reducing the cellular pool of GTP-bound Rac1 and Cdc42. The T6SS also increases the cellular pool of GTP-bound RhoA and decreases cofilin activity. These effects lead to abnormal actin polymerization causing collapse of lamellipodia and failure to retract the uropod. The T6SS also prevents the recruitment of soluble subunits of the NADPH oxidase complex including Rac1 to the BcCV membrane, but is not involved in the BcCV maturation arrest. Therefore, T6SS-mediated deregulation of Rho family GTPases is a common mechanism linking disruption of the actin cytoskeleton and delayed NADPH oxidase activation in macrophages infected with B. cenocepacia.
Roberto Rosales-Reyes; Alexander M Skeldon; Daniel F Aubert; Miguel A Valvano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-25
Journal Detail:
Title:  Cellular microbiology     Volume:  -     ISSN:  1462-5822     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-25     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:
© 2011 Blackwell Publishing Ltd.
Centre for Human Immunology, Department of Microbiology and Immunology and Department of Medicine, University of Western Ontario, London, ON N6A 5C1, Canada. Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México DF.
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