Identifying the Genetic Underpinnings that Drive the Transition of Commensal Yeast Microbes to Opportunistic Pathogens

The unique relationship between humans and commensal microbes is a critical component of human health. Recent studies have shown that this relationship can be altered by the microbial evolution of social behaviors. Biofilms are complex microbial communities that can be found in a variety of environments. The formation of biofilms plays a vital role in driving the virulence of many microbial pathogens that are capable of infecting humans, and has allowed these organisms to survive in hostile environments. In fact, many commensal microbes have evolved into virulent, opportunistic pathogens through this mechanism. Currently, there exist a number of studies on the genetic basis underlying this transition among bacterial species in clinical settings. However, research on the evolution of virulence in medically relevant fungal species is lacking. For my research project, I intend to investigate the genetic underpinnings that result in the transition of a commensal microbe to an opportunistic pathogen by tracking the genomic changes in particular phenotypes that play a role in virulence. Specifically, I will determine whether the genetic variants uncovered in  S. cerevisiae yeast strains isolated in a clinical environment are the same genetic variants that are selected for when virulence evolves de novo in the lab.

Well-known for its role in the fermentation of food and beverage, Saccharomyces cerevisiae (or, the budding yeast) is a useful model organism for tracking the genetic changes that allow for the transition to pathogenicity in fungal species. S. cerevisiae is capable of forming biofilms and adhering to each other and various surfaces. It is an emerging opportunistic pathogen and its biofilms have all the hallmark characteristics that reside in fungal biofilms. Furthermore, S. cerevisiae can be easily manipulated, and can be derived from numerous ecological and geographical niches, allowing for an abundance of genetic and phenotypic diversity. The particular phenotypes of S. cerevisiae that my project will focus on are the abilities to adhere to plastic and form biofilms in liquid culture, which have been previously revealed to be important mechanisms for opportunistic pathogenicity.

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