In order for successful fecal-oral transmission, enteric bacterial pathogens have to successfully compete with the intestinal microbiota and reach high concentrations during infection. Vibrio cholerae requires cholera toxin (CT) to cause diarrheal disease, which is thought to promote the fecal-oral transmission of the pathogen. Besides inducing diarrheal disease, the catalytic activity of CT also alters host intestinal metabolism, which promotes the growth of V. cholerae during infection through the acquisition of host-derived nutrients. Furthermore, recent studies have found that CT-induced disease activates a niche-specific suite of V. cholerae genes during infection, some of which may be important for fecal-oral transmission of the pathogen. Our group is currently exploring the concept that CT-induced disease promotes the fecal-oral transmission of V. cholerae by modulating both host and pathogen metabolism. Furthermore, the role of the intestinal microbiota in pathogen growth and transmission during toxin-induced disease merits further investigation. These studies open the door to investigating whether other bacterial toxins also enhance pathogen growth and transmission during infection, which may shed light on the design of novel therapeutics for intervention or prevention of diarrheal diseases.

Protein aggregates are a common feature of diseased and aged cells. Membrane proteins comprise a quarter of the proteome, and yet, it is not well understood how aggregation of membrane proteins is regulated and what effects these aggregates can have on cellular health. We have determined in yeast that the derlin Dfm1 has a chaperone-like activity that influences misfolded membrane protein aggregation. We establish that this function of Dfm1 does not require recruitment of the ATPase Cdc48 and it is distinct from Dfm1's previously identified function in dislocating misfolded membrane proteins from the endoplasmic reticulum (ER) to the cytosol for degradation. Additionally, we assess the cellular impacts of misfolded membrane proteins in the absence of Dfm1 and determine that misfolded membrane proteins are toxic to cells in the absence of Dfm1 and cause disruptions to proteasomal and ubiquitin homeostasis.