two-infection-assays-to-study-non-lethal-virulence-phenotypes-c

Two Infection Assays to Study Non-Lethal Virulence Phenotypes in <em>C. Albicans</em> using <em>C. Elegans</em>

While pathogens can be deadly to humans, many of them cause a range of infection types with non-lethal phenotypes. Candida albicans, an opportunistic ...

Emory University

 is an opportunistic fungal pathogen of humans that is typically diploid yet has a highly labile genome tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial for  to adapt to changing or stressful environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, in which tetraploids arise via diploid mating or stress-induced mitotic defects and undergo nonmeiotic ploidy reduction. However, it remains largely unknown how genetic background contributes to  genome instability  or in the host environment. Here, we tested how genetic background, ploidy, and the host environment impacts  genome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied across  strain background and ploidy state. We then assessed if host-induced genomic changes resulted in fitness consequences on growth rate and nonlethal virulence phenotypes and found that many host-derived isolates significantly changed relative to their parental strain. Interestingly, diploid host-associated  predominantly decreased host reproductive fitness, whereas tetraploid host-associated  increased host reproductive fitness. Together, these results are important for understanding how host-induced genomic changes in  alter its relationship with the host. is an opportunistic fungal pathogen of humans. The ability to generate genetic variation is essential for adaptation and is a strategy that  and other fungal pathogens use to change their genome size. Stressful environments, including the host, induce  genome instability. Here, we investigated how  genetic background and ploidy state impact genome instability, both  and in a host environment. We show that the host environment induces genome instability, but the magnitude depends on  genetic background. Furthermore, we show that tetraploid  is highly unstable in host environments and rapidly reduces in genome size. These reductions in genome size often resulted in reduced virulence. In contrast, diploid  displayed modest host-induced genome size changes, yet these frequently resulted in increased virulence. Such studies are essential for understanding how opportunistic pathogens respond and potentially adapt to the host environment.

Amanda C. Smith

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