Abstract
The pathogenic yeast Candida glabrata has become a public health issue due to the increasing number of echinocandin resistant clinical strains reported. In this study, acquisition and development of resistance to this antifungal class were studied in serial C. glabrata isolates from five patients admitted in two Spanish hospitals with a resistant profile against echinocandins associated with different mutations in hot-spot 1 of FKS2 gene. For two of these patients susceptible FKS wild-type isolates obtained prior to resistant ones were also investigated. Isolates were genotyped using multilocus sequence typing and microsatellite length polymorphism techniques, which yielded comparable results. Susceptible and resistant isolates from the same patient had the same genotype, being sequence type (ST) 3 the most prevalent among them. Isolates with different FKS mutations but the same ST were present in the same patient. MSH2 gene alterations were also studied to investigate their correlation with antifungal resistance acquisition but no association was found with antifungal resistance nor with specific genotypes. In vitro exposure to increasing concentrations of micafungin to susceptible isolates developed colonies carrying FKS mutations in agar plates containing a minimum concentration of 0.06 mg/L of micafungin after less than 48 h of exposure. We investigated the correlation between development of resistance and genotype in a set of susceptible strains after being in vitro exposed to micafungin and anidulafungin but no correlation was found. Mutant prevention concentration values and spontaneous growth frequencies after selection with both echinocandins were statistically similar, although FKS mutant colonies were more abundant after micafungin exposure (p < 0.001). Mutation S663P and F659 deletion were the most common ones found after selection with both echinocandins.
Highlights
MATERIALS AND METHODSInfections caused by Candida species, extensively referred to as candidiasis, have been described as the most common fungal disease globally (Pappas et al, 2018)
Candida albicans is the species causing the highest number of infections in clinical settings, an increasing prevalence of other Candida species has been reported in the last years, being Candida glabrata the second most common species isolated from invasive candidiasis in North America and central and northern countries in Europe (Pfaller et al, 2012; Asmundsdottir et al, 2013; Lortholary et al, 2014; Milazzo et al, 2014; Castanheira et al, 2016)
All strains isolated from Patients 3, 4, and 5 were echinocandin resistant, according to EUCAST breakpoints established for anidulafungin and micafungin
Summary
Infections caused by Candida species, extensively referred to as candidiasis, have been described as the most common fungal disease globally (Pappas et al, 2018). Candida albicans is the species causing the highest number of infections in clinical settings, an increasing prevalence of other Candida species has been reported in the last years, being Candida glabrata the second most common species isolated from invasive candidiasis in North America and central and northern countries in Europe (Pfaller et al, 2012; Asmundsdottir et al, 2013; Lortholary et al, 2014; Milazzo et al, 2014; Castanheira et al, 2016). An ever-growing number of echinocandin resistant clinical isolates have been reported worldwide in the last years and population studies in the United States and Denmark have shown an increase in echinocandin resistance rate (Alexander et al, 2013; Farmakiotis et al, 2014; Vallabhaneni et al, 2015; Astvad et al, 2017), which is conferred by the presence of point mutations in specific regions (denominated as hot-spots) of FKS genes, which encode this enzyme’s catalytic subunits (Katiyar et al, 2012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
