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.