New insights into the echinocandin resistance in Candida spp. in the clinical setting

Abstract

Despite a huge consumption of echinocandins, the emergence of resistance in Candida spp has remained overall limited. Here, we depicted the epidemiology of Candida spp in our center face to the echinocandins consumption. We postulate new hypotheses that may explain the shaping of candines resistance in the clinical setting. Epidemiology of Candida infections and echinocandin consumption were evaluated in our center over 12 years (2006-2018). Glucan synthase genes (fks1, fks2) were sequenced. The in vitro fitness was assessed for couple of isogenic strains, of which one was resistant. Finally, the modelling of Candida FKS proteins was realized. Despite a three-fold increase in echinocandin consumption, no significant emergence of resistance was observed. In Candida albicans, fks1 mutations affect the three-dimensional conformation of the glucan synthase, which may result in altered export of the glucan chain, which could explain the observed reduced fitness. In contrast, cross-complementation between FKS1 and FKS2 in Nakaseomyces glabratus might circumvent the negative impact on fitness. ConclusionsOur results support the fact that N. glabratus is more prone to the spread of echinocandin-resistant strains. The link between mutations in the glucan synthase and fitness of Candida strains might explain the difference in the species-specific emergence of echinocandins-resistant strains.