All of these mechanisms represent models for bacterial pathogenesis and interaction with the host in general. Our laboratory focuses on the molecular mechanisms of adherence with respect to colonization, protein secretion with respect to the elaboration of adherence factors and toxin, and coordinate expression of the corresponding genes. Our goals are to understand the processes in enough detail to design better methods to control infection by defining immunogens for improved vaccine development, improving ways to grow strains for manufacture of killed whole cell vaccines, and by identifying new targets to be considered for the design of novel antibiotics. The research projects in our lab can be divided into two broad areas. The first deals with interaction between the bacterium and the host.
Bacteria colonize hosts through the use of surface appendages termed fimbriae or pili.
Vibrio cholerae potentially utilizes several pili types and outer membrane proteins for this process. All of these represent potential immunogens. We have focused on a pilus termed TCP for toxin coregulated pilus. For this structure, we employ molecular biology and immunology techniques to investigate the function of specific domains in the colonization process, and the efficacy for their use as vaccine components. Aspects of the pilus study also involve the macromolecular assembly of this structure by studying the functions of various cloned gene products.