Biochemical and genetic analysis of secretory outer membrane vesicles produced by pathogenic bacteria.
Pathogenic bacteria use membrane vesicles as a means to secrete toxins and to contact host cells and tissues. The incorporation of different types of cellular material into vesicles is an outstanding system for studying both directed secretory pathways and mechanisms of bacterial virulence. Trainees in my lab biochemically evaluate vesicles produced by virulent human pathogens that contribute to a large proportion of worldwide cases of diarrhea and to disease in patients with cystic fibrosis: enterotoxigenic E. coli and Pseudomonas aeruginosa.
We are investigating the mechanism by which cellular material is brought to the sites of vesicle budding, the requirements for vesicle production, and the fate of the incorporated material in relation to the virulence of the parent organism. We are also identifying bacterial genes that influence the production of vesicles and have characterized members of an envelope stress pathway that regulate vesicle production. It is hoped that these studies will lead to the identification of therapeutic targets in these organisms. Since vesicle production is a ubiquitous process, the comparison of vesicle secretion in different organisms may reveal conserved general secretory mechanisms employed by many different Gram-negative pathogens.