Burkholderia cenocepacia disrupts host cell actin cytoskeleton by inactivating Rac and Cdc42.
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.
Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Ronald S
RS
Flannagan
Valentin
V
Jaumouillé
Kassidy K
KK
Huynh
Jonathan D
JD
Plumb
Gregory P
GP
Downey
Miguel A
MA
Valvano
Sergio
S
Grinstein
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D057508:Burkholderia cenocepacia / Q000472:pathogenicity*; D002478:Cells, Cultured; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D010587:Phagocytosis; D010873:Pinocytosis; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors*
C107953:RAC1 protein, human; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein