Abstract
ABSTRACTHere, we report two paired sets of an index wild-type Candida glabrata bloodstream isolate and subsequent echinocandin-resistant FKS mutant. One paired set exhibited a higher proportion of clumping cells and was more virulent in the invertebrate host Galleria mellonella than the other paired set. No virulence difference between the paired index and FKS strains was observed. These findings imply a potential link of clumping morphology with virulence in C. glabrata that is uncoupled from FKS-mediated echinocandin resistance.IMPORTANCE Candida glabrata is a leading cause of invasive candidiasis. In contrast to other species, it has a high propensity for developing resistance to echinocandins, which are the first-line treatment. Unlike the dimorphic Candida albicans which can grow invasive filamentous hyphae, C. glabrata lacks this ability. Here, we report a link between virulence and clumping cell morphology in two different sets of clinical C. glabrata strains obtained from patients failing echinocandin therapy. One set of paired strains (echinocandin-susceptible and subsequent resistant mutant) had a high proportion of clumping cells in the population and were significantly more virulent than another set which had fewer clumping cells. Additionally, we corroborate that echinocandin resistance does not impart a significant fitness cost. Our findings suggest that clumping morphology may be an important but previously underestimated virulence factor for C. glabrata and also aid our understand for the high prevalence of resistance observed in this species.
Highlights
Despite the widespread use of echinocandins, acquired resistance remains uncommon in most Candida species (;3%) [1], whereas a relatively high rate of Candida glabrata isolates (.10%) display echinocandin resistance [2,3,4,5]
Doubling time (h) aCell wall chitin was analyzed via indirectly measuring the fluorescence intensity of calcofluor white (CFW)-stained C. glabrata, with arbitrary units (AU)
An analysis of whole-genome shotgun sequencing data showed that paired strains were highly related, with significantly fewer single nucleotide polymorphism (SNP) differences observed between intrapatient (69 to 84 SNPs) versus interpatient (4,580 to 4,644 SNPs) isolates
Summary
Chenlin Hu Gary Fong Sebastian Wurster Dimitrios P. Follow this and additional works at: https://digitalcommons.chapman.edu/pharmacy_articles. Comments This article was originally published in Microbiology Spectrum, volume number, issue number, in year.
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