Physiology of outer membrane vesicles in Vibrio cholerae

The release of outer membrane vesicles (OMVs) is a common feature of Gram-negative bacteria, but information on their physiological roles is still limited. Recently, we have identified a conserved OMV release mechanism in Gram-negative bacteria, which relies on accumulation of phospholipids in the outer membrane. In fact, Gram-negative bacteria can control the OMV levels by transcriptional activation or repression of a retrograde phospholipid transporter (VacJ/Yrb-system). As the system is highly conserved in Gram- negative bacteria it is present and functional in our model organism Vibrio cholerae, the causative agent of cholera disease. As a facultative human pathogen, V. cholerae transits between the aquatic reservoir and the human gastrointestinal tract. Adaptation to different stages of its lifecycle requires efficient modulation of the outer membrane. We hypothesize that OMV release can be a versatile adaptation mechanism allowing a (i) rapid surface exchange & (ii) delivery of effectors associated to OMVs to host cells. Indeed, current data of our laboratory indicates that V. cholerae increases vesiculation upon host entry, which facilitates in vivo fitness. The impact of OMV release on in vivo fitness will be addressed in the first activity. In the second activity, we will investigate the pathophysiological role and fate of OMVs after release from the bacterial membrane. First results indicate that V. cholerae OMVs are readily taken up by intestinal epithelial cells and could modulate host cell physiology. In summary, results obtained within this proposed work should improve our understanding on the patho-physiological roles of V. cholerae OMVs. It is likely that our findings can also be extended to other bacteria.