Kennedy Agwamba
Candida albicans, a common commensal of humans and the most frequently isolated opportunistic fungus, is commonly found in the oral, gastrointestinal and genitourinary tracts, where its presence is thought to be generally benign. These natural reservoirs act to seed systemic infections, particularly in immunocompromised individuals, where C. albicans infects many of the major organs in the body. Such infections are life-threatening, and even with antifungal treatment the associated mortality rate is 20-40%. In many microbial pathogens, the serial propagation of a strain within the host has been shown to increase the strain’s virulence. However, most C. albicans isolates are well adapted to the mammalian environment, hindering microevolution events that could result in increased fitness or virulence. We hypothesized that extended passaging of clinical isolates of C. albicans would more readily allow the identification of novel fitness and virulence factors. There is limited knowledge around the microevolution of genes associated with pathogenicity in these cases, and our goal was to characterize the genetic differences between these pre-passaged and passaged strains of C. albicans. For our analysis, we used next-generation sequencing data generated on the Illumina HiSeq platform to study how clinical isolates of three C. albicans strains changed following passaging. Reads from pre-passaged and passaged isolates were aligned to the C. albicans SC5314 reference using Burrows-Wheeler Aligner; single nucleotide polymorphisms, insertions, and deletions were detected using the Genome Analysis ToolKit UnifiedGenotyper. We uncovered a number of initial candidate virulence factors, including transcriptional regulators of zinc cluster DNA-binding motif, putative GPI-anchored proteins, and ALS family proteins. These results present potential targets for antifungal treatments, which may prove valuable for the future development of antifungal drugs.
PROJECT: Genomic analysis of Candida albicans following serial passage identifies candidate virulence factors
Mentors: Rhys Farrer and Christina Cuomo, Genome Sequencing and Analysis Program
The Summer Research Program in Genomics at the Broad Institute was a truly enriching experience. The program nurtured me and helped me become a better scientist by challenging me to conduct cutting-edge research to explore ambitious questions, and by encouraging me to improve the person behind the science. I learned as much about myself as I did about science.
