The long-term goal of my research program is to help develop a safe and effective vaccine against enterotoxigenic Escherichia coli (ETEC). Globally, ETEC is one of the top five diarrhea causing pathogens. Most ETEC-attributable morbidity and mortality occurs in low- to middle-income countries in the developing world. ETEC is transmitted via the fecal-oral route by eating or drinking contaminated food or water. Vaccine development to ETEC is hindered by heterogeneity among ETEC isolates. There are over 100 different ETEC serotypes with further genetic and phenotypic variations in toxin and colonization factor expression. ETEC encode one of two toxins, namely the heat-labile toxin (LT) and/or the heat-stable toxin (ST). Each toxin alone can cause severe secretory diarrhea. Our current research program is geared at understanding why a percentage of ETEC isolates expend the metabolic energy to encode and produce both LT and ST (i.e. Is there an evolutionary (dis)advantage to strains that produce both toxins?). We seek to understand how ST promotes ETEC pathogenesis using in vitro, cell culture, and animal models.
Another goal of my laboratory is aimed at developing a safe and effective ST-toxoid vaccine candidate. Since ST is small (~2 kD), it is not immunogenic. We are pursuing conjugation chemistry and other delivery systems to make ST and ST-toxoids immunogenic for inclusion into current pipeline ETEC vaccines.
I am also interested in elucidating other virulence properties of ETEC including biofilm-formation and antimicrobial resistance. Biofilms are natural mucoadhesive extracellular matrices and are more resistant to oxidative and acid stress and antibiotics than their planktonic counterparts.
