Host/Candida Interactions in Health and Disease
The goal of our research is to understand how the fungus Candida albicans interacts with its host during both normal colonization and invasive disease. C. albicans is a benign commensal that normally colonizes humans. As a commensal, the organism colonizes the gastrointestinal tract, skin and genitourinary tract of a human host for long periods of time without causing disease. However, if the host becomes immunocompromised, colonizing fungal organisms produce the characteristic invasive lesions associated with candidiasis. Under these conditions, C. albicans is capable of causing life-threatening infection.
Through our studies we seek to answer the following questions:
- What factors determine the population size of C. albicans in the intestinal tract of a healthy host?
- How do colonizing cells adapt to the environment that is encountered in the intestinal tract?
- What environmental cues stimulate invasive growth of C. albicans into host tissue?
- What protein factors are involved in the response of cells to cues from the environment?
To understand C. albicans activities that promote commensal colonization, gene expression by C. albicans during colonization is being studied. Results to date reveal features of the host that are important for control of C. albicans gene expression and C. albicans transcription factors that regulate gene expression in this environment. Some genes that are important for bloodstream infection are not important for intestinal colonization and vice versa. Therefore, different genes play roles in different host niches.
It is believed that morphological conversion of yeast-form cells to filamentous hyphal forms is important in order for the organism to grow invasively within the tissues of its host during disease. Numerous cues from the environment promote hyphal development.We have found that C. albicans senses and responds to contact with a semi-solid matrix such as agar.
Figure 1. The section shown in A illustrates invasive growth in vivo; the image shown in B illustrates how contact with a semi-solid matrix results in the development of filaments.
Contact with an agar matrix results in activation of MAP kinase signaling pathways that promote development of invasive filaments. The mechanism of contact sensing and MAP kinase activation is under investigation.