Blood cultures contain populations of genetically diverse Candida albicans strains that may differ in echinocandin tolerance and fitness

Abstract

Background It is unknown whether within-patient Candida albicans diversity is common during bloodstream infections (BSIs). Methods We determined whole genome sequences of 10 C. albicans strains from blood cultures (BCs) in each of 4 patients. We performed detailed phenotypic studies on strains from 1 patient. Results BCs in 3 patients contained mixed populations of strains that differed by large-scale genetic variants, including chromosome (Chr) 5 or 7 aneuploidy and Chr1 loss of heterozygosity (n=1 each). In patient M, Chr7 trisomy (Tri7) strains were attenuated for hyphal and biofilm formation in vitro, due at least in part to NRG1 over-expression. Nevertheless, representative Tri7 strain M1 underwent filamentation during disseminated candidiasis (DC) in mice. M1 was more fit than euploid strain M2 during DC and mouse gastrointestinal colonization, and in blood ex vivo. M1 and M2 exhibited identical echinocandin minimum inhibitory concentrations, but M2 was more tolerant to micafungin in vitro. Furthermore, M2 was more competitive with M1 in mouse kidneys following micafungin treatment than it was in absence of micafungin. Tri7 strains represented 74% of patient M’s baseline BC population, but euploid strains were 98% of the population after 3d of echinocandin treatment. Findings suggest that echinocandin tolerant, euploid strains were a subpopulation to more fit Tri7 strains at baseline and then were selected upon echinocandin exposure. Conclusions BCs in some patients are comprised of diverse C. albicans populations not recognized by the clinical lab, rather than single strains. Clinical relevance of C. albicans diversity and echinocandin tolerance merits further investigation.