UC Merced

Candida albicans is a commensal member of the human microbiota that is also capable of causing superficial and disseminated infections and is known to be the predominant fungal pathogen of humans in clinical settings. Mucosal linings are critical for protecting the host against infections, and it is the biological and viscoelastic properties of mucus, predominantly attributed to glycoproteins called mucins, that provide this protection. Chapter 1 introduces how mucins are involved in maintaining a healthy microbial balance on mucosal linings when directly interacting with microorganisms. Oftentimes, invading microorganisms colonize mucosal surfaces by forming microbial communities called biofilms. Biofilms can have detrimental impacts on the host because, once formed, they are highly resistant to chemical and mechanical perturbations. Chapter 2 aims to discover novel regulators that mediate the ability of C. albicans to interact with mucin in the context of biofilms. We screened a library of 211 transcription factor deletion mutants using in vitro biofilm assays in the presence of mucin to identify the regulators involved in governing C. albicans interactions with mucin. A total of 12 “master” regulators were found to play roles in interacting with mucins. Using a combination of genetic and genome-wide approaches, we mapped the regulatory connections of each transcription factor to one another and to downstream target genes to determine the regulatory network controlling the ability of C. albicans to interact with mucin. Understanding how C. albicans modulates its interactions with mucin will shed new light on the regulatory control that evolved to mediate this important interaction with the host. In Chapter 3, we introduce a host-pathogen model system to study the interactions between C. albicans and the flatworm Schmidtea mediterranea. This model is a unique invertebrate model that allows for the study of an early C. albicans epithelial infection in the presence of secreted mucus produced by the flatworm. Using this model, we identified two C. albicans proteins that mediate epithelial infection in S. mediterranea as well as a comprehensive host response facilitated by diverse host tissues to clear the infection.