Document Detail


Burkholderia cenocepacia disrupts host cell actin cytoskeleton by inactivating Rac and Cdc42.
MedLine Citation:
PMID:  22023324     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Burkholderia cenocepacia, a member of the Burkholderia cepacia complex, is an opportunistic pathogen that causes devastating infections in patients with cystic fibrosis. The ability of B.  cenocepacia to survive within host cells could contribute significantly to its virulence in immunocompromised patients. In this study, we explored the mechanisms that enable B. cenocepacia to survive inside macrophages. We found that B. cenocepacia disrupts the actin cytoskeleton of infected macrophages, drastically altering their morphology. Submembranous actin undergoes depolymerization, leading to cell retraction. The bacteria perturb actin architecture by inactivating Rho family GTPases, particularly Rac1 and Cdc42. GTPase inactivation follows internalization of viable B. cenocepacia and compromises phagocyte function: macropinocytosis and phagocytosis are markedly inhibited, likely impairing the microbicidal and antigen-presenting capability of infected macrophages. The type VI secretion system is essential for the bacteria to elicit these changes. This is the first report demonstrating inactivation of Rho family GTPases by a member of the B.  cepacia complex.
Authors:
Ronald S Flannagan; Valentin Jaumouillé; Kassidy K Huynh; Jonathan D Plumb; Gregory P Downey; Miguel A Valvano; Sergio Grinstein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-15
Journal Detail:
Title:  Cellular microbiology     Volume:  14     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-19     Completed Date:  2012-05-10     Revised Date:  2012-11-30    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  239-54     Citation Subset:  IM    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
Affiliation:
Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / metabolism*
Animals
Burkholderia cenocepacia / pathogenicity*
Cells, Cultured
Humans
Macrophages / microbiology*
Mice
Phagocytosis
Pinocytosis
cdc42 GTP-Binding Protein / antagonists & inhibitors*
rac1 GTP-Binding Protein / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/RAC1 protein, human; EC 3.6.5.2/cdc42 GTP-Binding Protein; EC 3.6.5.2/rac1 GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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