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.

Status: Epub ahead of print Type: Journal Article PubMed ID: 41026105

• To find other papers on a gene and topic, click on the colored ball in the appropriate box.
  displays other papers with information about that topic for that gene.
  displays other papers in CGD that are associated with that topic.
  The topic is addressed in these papers but does not describe a specific gene or chromosomal feature.


• To go to the Locus page for a gene, click on the gene name.