Manipulation of host cell signaling by bacterial FIC proteins

Abstract

Fic proteins are found in all kingdoms of life and are defined by their conserved FIC domain that catalyzes the transfer of an AMP moiety onto target proteins. A subset of Fic proteins has been shown to adenylylate small GTPases of the Ras superfamily resulting in their inactivation leading to cytoskeletal collapse and cell death. Pathogens belonging to the genus Bartonella translocate effector proteins into the host cell cytoplasm in order to establish chronic infections. As most of these effectors harbor a FIC domain, our lab is studying its role in bacterial pathogenesis by identifying targets in the eukaryotic host cell. Here, we present an example of highly selective adenylylation among the class of small GTPases. In contrast to other previously described Fic proteins, we found that Bep1 of Bartonella rochalimae does not adenylylate a broad spectrum of Rho family GTPases but exclusively targets Rac1 indicating a more subtle subversion of cellular functions which is consistent with the stealthy infection strategy of Bartonella. We hypothesize that Rac1 adenylylation leads to cytoskeleton rearrangements promoting bacterial entry and survival. Research was supported by SNSF grant 31003A‐132979 and Werner Siemens Foundation.