Genomic epidemiology of Candida pathogen causing candidaemia 

Candidemia is a severe yeast bloodstream infection associated with high morbidity and mortality rates despite antifungal therapy. Recently WHO has published the Fungal Priority Pathogens List, in which Candida auris is listed in the “critical priority” group, while C. parapsilosis, and C. glabrata are classified as “high priority” group. Despite the importance of candidaemia, Candida genetic variation and drug resistance mechanisms are not well understood due to the lack of comprehensive whole genome sequencing (WGS) studies at a global scale. We have been studying the epidemiology and antifungal susceptibilities of major Candida pathogens in the Middle East and SE Asia using WGS approach. Genomic analysis revealed low genetic variability among Candida auris isolates from COVID-19 patients in Qatar, indicating a clonal outbreak and ongoing dissemination of Clade I C. auris among healthcare facilities. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions; Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility. While in C. glabrata, data illustrated diverse genetic profiles, and evidence of recombination among the Qatar strains. Results demonstrated nosocomial transmission and global circulation of major clade I genotypes. Known and novel SNPs were identified as associated with antifungal resistance. In contrast, at the C. glabrata population level, signatures of recombination, and both MATa and MATa alleles were detected, indicating the potential for sexual reproduction in clinical populations. Also, the similarity between the C. glabrata populations in Qatar and other parts of the world illustrated that recent anthropogenic activities play a significant role in shaping population structure.