Candida albicans is one of the major eukaryotic members of the human microbiome, where it resides in a complex environment populated by host cells and other microbes. The predominant growth form of many microorganisms, including C. albicans, is a biofilm. A C. albicans biofilm is a community of multiple cell types, including both yeast and hyphal cells, which are adhered to one another in a dense structure surrounded by an extracellular matrix composed largely of protein, sugars, and nucleic acids. The cells in biofilms express a distinct genetic program from that found in free-floating cells, which results in differential attributes such as drug resistance, adherence, and resistance to perturbation.
This body of work focuses on two areas of biofilm formation, the transcriptional control of biofilm formation over time and the interspecies interactions in mixed C. albicans and bacterial biofilms. First, we identify three new regulators of biofilm formation, some of which are required only at particular time periods during development. We also measure gene expression during development and identify transcriptional patterns of interest in genes that encode adhesion and metabolic proteins, expanding our understanding of how biofilms change over time and compare to cells grown in suspension cultures. Second, we discover that C. albicans interacts with several species of bacteria in multiple ways. Three species, K. pneumoniae, E. coli, and E. faecalis, induce expression of WOR1, which encodes the master transcriptional regulator of the white - opaque switch in C. albicans. Two anaerobic species, C. perfringens and B. fragilis, are able to grow within the C. albicans biofilm in ambient oxic conditions, which are normally toxic to these species. We demonstrate that the interior of the biofilm is hypoxic, which likely contributes to anaerobe survival and proliferation. C. perfringens additionally induces clumping of C. albicans cells in suspension culture, forming structures resembling mini-biofilms, which are protective of C. perfringens cells and the formation of which relies on the genetic program controlling biofilm formation.
Our work demonstrates that C. albicans biofilms are spatially heterogenous structures that are dynamic during development, and highlights the importance of microenvironments in supporting the survival of human microbiome members.
