BEP-1, a Brucella VirB effector that promotes cortical actin reorganization

MARCHESINI, MARÍA INÉS; DIEGO J. COMERCI; RODOLFO A. UGALDE

San Miguel de Tucumán, Argentina

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2009

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

Brucella abortus is an intracellular pathogen that replicates inside mammalian cells. A type IV secretion system (VirB) is essential to subvert lysosome fusion and to create an organelle that supports Brucella replication inside host cells. Translocation of effector proteins via VirB likely modulates host vesicular traffic, allowing the biogenesis of the endoplasmic reticulum-derived replicative organelle. Translocation of potential substrates into host cells was assayed using the Bordetella pertussis Adenylate Cyclase (CyaA) fusion approach. A B. abortus protein that is translocated to the host cell via VirB was identified and called BEP-1. We could also determine that substrate recognition by VirB machinery involves an N-terminal translocation signal. BEP-1 shows similarity to the helix domain of the eukaryotic protein cortactin. Cortactin is an actin-binding protein and a central regulator of the actin cytoskeleton. It has been involved in many cellular processes including cortical actin assembly, endocytosis, and cell migration. Importantly, cortactin is also a common target exploited by many microbes during infection. Interestingly, BEP-1 ectopically expressed in HeLa cells promotes lamellipodia formation and colocalizes with cortical actin and cortactin, suggesting that the identified VirB substrate might be interacting with the host cell actin cytoskeleton.