Contact sensing and C. albicans-host interaction

Kumamoto, Carol

Abstract

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 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 more than one component that promotes invasiveness. The phenotypes of such mutants during laboratory agar invasion will be studied. To understand how the contact sensing process takes place, Aim 3 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.

Public Health Relevance

Hospitalized patients experience many of the factors that predispose patients to Candida infection such as immunosuppression, violation of barriers, and use of broad spectrum antibacterial drugs. Therefore, Candida spp., particularly Candida albicans, are an important cause of nosocomial infection. Infection by C. albicans is characterized by growth of the organism into the tissues of its host. This research project seeks to understand C. albicans activities that are necessary for the growth of the organism into host tissue. Understanding how C. albicans cells are able to grow into host tissue and how the organisms sense the presence of tissue in their environment will aid in the development of future therapies aimed at blocking invasive growth into tissue.