TRUSTEES OF TUFTS COLLEGE INC
This research project investigates the mechanisms used by the opportunistic fungal pathogen, Candida albicans to produce disease. The long term goal of this research is to understand how C. albicans cells cause infection. Environmental sensing is likely to be important for regulation of activities that promote virulence, such as the ability of C. albicans cells to convert into invasive filamentous hyphae, which penetrate into host tissue. Studies of invasiveness under laboratory conditions have shown that C. albicans cells sense contact with a semi-solid matrix, causing them to produce invasive hyphae. A plasma membrane protein that is needed for invasive growth in response to contact with agar medium and may be a sensor of contact has been characterized. To evaluate the importance of contact sensing for invasion during infection, a mutant lacking the sensor will be studied in several animal models of infection (Aim 1). Preliminary studies suggest that other plasma membrane proteins also participate in contact sensing. Aim 2 will focus on analyzing double or triple mutants lacking several components that are important for invasiveness. The phenotypes of such mutants during laboratory agar invasion and during growth in animal models of infection will be studied.
Also, a mutant lacking a contact sensing protein was found to be hypersusceptible to cell wall acting compounds. Aim 3 will test whether mutants of this type are hypersusceptible during animal infection. To understand how the contact sensing process takes place, Aim 4 will seek to
identify and characterize binding partners that function with the contact sensing protein. These studies will increase the understanding of regulatory mechanisms that are important in C. albicans pathogenesis.