| The overall scope of my thesis project is to determine effects of farnesol, a secreted factor produced by C. albicans, on P. aeruginosa virulence. These two organisms are frequently found with one another in mixed infections and our lab has previously determined that they affect each other in numerous ways. I have found that farnesol, a secreted factor produced by C. albicans, can decrease virulence factor regulation in P. aeruginosa, by interacting with PqsR, a global virulence factor regulator. P. aeruginosa clinical isolates can be divided into a number of different classes (phenotypic and genetic) based on acquired heritable mutations. In a subset of strains isolated from Cystic Fibrosis (CF) patients, I have found that farnesol increases virulence factor production. This subset shares a common loss-of-function mutation in the LasR transcriptional regulator, and when grown in the presence of farnesol, there is an increase in the production of PQS, a key virulence factor regulator. We have been able to confirm the phenotype using a non-polar PA14DeltalasR mutant. Using the non-polar lasR mutant, it was demonstrated that the increase in PQS production by farnesol is due to the upregulation of pqsH transcription, which is dependent on RhlR and the canonical PQS biosynthetic and regulatory pathway. The increase in PQS production can be inhibited by the addition of an oxidative stress protectant, suggesting that farnesol is inducing oxidative stress in the bacterium. The work presented here examines the complex multispecies interaction, with the attempt to characterize the interaction at the molecular and mechanistic level, which when understood can aid in the development of better treatments for P. aeruginosa or C. albicans infections. |
