Paradoxical effect to caspofungin in Candida species does not confer survival advantage in a Drosophila model of candidiasis

The paradoxical growth (PG) to echinocandins has been observed in vitro in Candida and Aspergillus species. Its mechanisms are incompletely understood, although activation of calcineurin and chitin biosynthesis pathways have been implicated. Importantly, the in vivo relevance of PG is not well defined as there is paucity of both animal model and clinical data on the implications of this phenomenon. As PG in vivo has been studied in the context of echinocandin exposure, it remains unknown whether there are differences in virulence of Candida strains showing or not showing PG when they infect the host in the absence of echinocandin pressure. To that end, we examined differences in virulence of Candida isolates showing or not PG in our Tolldeficient fly model of candidiasis, a model we have shown good concordance with mouse models of candidiasis. We used 20 clinical bloodstream isolates: 10 Candida albicans (5 with PG to caspofungin, 5 without PG) and 10 C. tropicalis (5 with PG, 5 without PG). All isolates had comparable growth in vitro in the absence of caspofungin (data not shown). We used female Oregon Toll-deficient flies and followed standard procedures for feeding, housing and manipulation of flies. The flies were exposed to a 12-h light/dark cycle. All Candida strains were grown on yeast-peptone-dextrose (YPD) agar medium. For the infection experiments, cultures of each strain were grown overnight at 30 °C on YPD liquid medium before collection of yeast-cells, which were Paradoxical effect to caspofungin in Candida species does not confer survival advantage in a Drosophila model of candidiasis