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Candida auris  is an emerging yeast pathogen of candidemia with the ability to develop resistance to all current antifungal drug classes. Novel antifungal therapies against  C. auris  are warranted. NSC319726 is a thiosemicarbazone with an inhibitory effect on fungal ribosome biogenesis that has demonstrated some antifungal activity. In this study, we assessed the  in vitro  activity and  in vivo  efficacy of NSC319726 against  C. auris . NSC319726 was active  in vitro  against 22  C. auris  isolates from different clades, with MICs ranging from 0.125 to 0.25 mg/liter. Despite complete visual growth inhibition, the effect was described as fungistatic in time-kill curves. Interactions with fluconazole, amphotericin B, and micafungin, as tested by the checkerboard dilution method, were described as indifferent. NSC319726 demonstrated significant effects in rescuing  G. mellonella  larvae infected with two distinct  C. auris  isolates, compared to the untreated group. In conclusion, NSC319726 demonstrated  in vitro  activity against  C. auris  and  in vivo  efficacy in an invertebrate model of infection. Its potential role as a novel antifungal therapy in humans should be further investigated.   IMPORTANCE   Candida auris  is emerging as a major public health threat because of its ability to cause nosocomial outbreaks of severe invasive candidiasis. Management of  C. auris  infection is difficult because of its frequent multidrug-resistant profile for currently licensed antifungals. Here, we show that the thiosemicarbazone NSC319726 was active  in vitro  against a large collection of  C. auris  isolates from different clades. Moreover, the drug was well tolerated and effective for the treatment of  C. auris  infection in an invertebrate model of  Galleria mellonella . We conclude that NSC319726 might represent an interesting drug candidate for the treatment of  C. auris  infection.

Assessment of the In Vitro and In Vivo Antifungal Activity of NSC319726 against Candida auris