Decoding Candida albicans' molecular basis of host-microbe interactions that foster commensalism and pathogenesis
Among the estimated five million fungal species on Earth, Candida albicans stands out as a remarkable exception — a lifelong human associate that can live harmlessly as part of the gastrointestinal microbiome, yet also emerge as the most common fungal pathogen. We hypothesize that this intimate, enduring partnership with its host has driven the evolution of specialized fungal programs enabling C. albicans to thrive across a wide variety of human niches.
Our laboratory’s central mission is to define the molecular basis of host–microbe interactions that foster both commensalism and pathogenesis.
To approach these questions, we harness a broad toolkit: genetic engineering, animal models of both commensalism and disease, and high-resolution molecular approaches such as whole-genome chromatin immunoprecipitation and high-throughput sequencing. To date, we have identified a series of novel virulence factors that act independently of the yeast-to-hyphal transition, which was previously thought to be this species’ major virulence specialization (Noble et al., Nature Genetics 2010). Our detailed characterization of the Sef1 virulence factor uncovered a C. albicans-specific transcriptional network whose activity has opposite roles in commensalism and disseminated infections (Chen et al., Cell Host and Microbe 2011; Chen and Noble, PLoS Pathogens 2012).
More recently, we discovered that passage of C. albicans through the mammalian gastrointestinal milieu triggers a developmental switch to a commensalism-specific cell type (Pande et al., Nature Genetics 2013). This morphological and functional plasticity — the ability to shift between specialized cell states optimized for different host environments — helps explain C. albicans' extraordinary success in colonizing humans and its versatility. Decoding these switching mechanisms offers opportunities for new treatment and prevention strategies of clinical infectious diseases.