TcpF Is a Soluble Colonization Factor and Protective Antigen Secreted by El Tor and Classical O1 and O139 Vibrio cholerae Serogroups

Vibrio cholerae causes diarrhea by colonizing the human small bowel and intoxicating epithelial cells. Colonization is a required step in pathogenesis, and strains defective for colonization are significantly attenuated. The best-characterized V. cholerae colonization factor is the toxin-coregulated pilus (TCP). It has been demonstrated that TCP is required for V. cholerae colonization in both humans and mice. TCP enhances bacterial interactions that allow microcolony formation and thereby promotes survival in the intestine. We have recently discovered that the TCP biogenesis apparatus also serves as a secretion system, mediating the terminal step in the extracellular secretion pathway of TcpF. TcpF was identified in classical isolates of V. cholerae O1 as a soluble factor essential for colonization in the infant mouse cholera model. In the present study, we expanded our analysis of TcpF to include the O1 El Tor and O139 serogroups and investigated how TCP and TcpF act together to mediate colonization. Additionally, we demonstrated that antibodies generated against TcpF are protective against experimental V. cholerae infection in the infant mouse cholera model. This observation, coupled with the fact that TcpF is a potent mediator of colonization, suggests that TcpF should be considered as a component of a polyvalent cholera vaccine formulation.