A bacterial protein induces holes for migration.

Staphylococcus aureus inactivates RhoA to open tunnels through endothelial cells, report Boyer et al. (page 809). These “macroapertures” may allow the pathogenic bacteria easy access to the endothelial basement membranes for tissue invasion and colonization.

Numerous bacterial virulence factors, including EDIN, target proteins in the Rho GTPase family, deregulating the actin cytoskeleton and changing cell shape and adhesion. EDIN is an ADP–ribosyltransferase that locks RhoA in an inactive state.

Boyer et al. found that when endothelial cells in culture or in rat arteries were exposed to S. aureus expressing EDIN or to recombinant EDIN protein, macroapertures formed in a dose- and time-dependent manner. The timing and number of macroapertures correlated with RhoA–ADP–ribosylation.

Without active RhoA, the actin cytoskeleton was rearranged with a loss of stress fibers. The macroapertures appeared as a result of retraction of the membrane and were not associated with tears or wounds in the membrane.

Once a macroaperture formed, the cell appeared to detect the problem. A dense meshwork of actin encircled the opening and lamellipodium-like structures formed at the edges leading to closure. Therefore, the openings only lasted a few minutes, but that is more than enough time for bacteria to access the basement membrane.

Researchers reported recently that as leukocytes move from the bloodstream to surrounding tissues they can induce similar openings in endothelial cells in a Rho-dependent manner. Pathogenic bacteria may have co-opted this system for more nefarious purposes.