Research in my lab has focused on the interaction of bacterial virulence factors with immune defenses, with a strong emphasis on the role of bacterial toxins. I have had a longtime interest in the toxins produced by Bordetella pertussis, the causative agent of whooping cough. Pertussis toxin is essential for virulence. This toxin disrupts cellular communication mediated by GTP-binding proteins, and has a profound influence on the ability to mount an effective immune response. Interestingly, on the positive side, pertussis toxin can inhibit HIV replication in T cells and we are currently studying the molecular basis for this phenomenon. A second toxin produced by B. pertussis, the adenylate cyclase toxin is also essential for virulence. This toxin acts by poisoning the ability of neutrophils to phagocytose the bacteria. Phagocytosis of B. pertussis can only occur in the presence of neutralizing antibodies to adenylate cyclase toxin. Directing the immune response to produce neutralizing antibodies to adenylate cyclase toxin could improve pertussis vaccine efficacy.
We are actively examining assembly and secretion of pertussis toxin and another AB5 toxin, Shiga toxin, produced by E. coli O157:H7. Interestingly, Shiga toxin is encoded by a lysogenic bacteria phage and Shiga toxin secretion is mediated by viral lysis of the E. coli host. Studies are underway to understand the in vivo signals that promote Shiga toxin expression and release from the bacteria.