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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_A88593023DD0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Assessment of the In Vitro and In Vivo Antifungal Activity of NSC319726 against Candida auris.
Journal
Microbiology spectrum
Author(s)
Li J., Coste A.T., Bachmann D., Sanglard D., Lamoth F.
ISSN
2165-0497 (Electronic)
ISSN-L
2165-0497
Publication state
Published
Issued date
22/12/2021
Peer-reviewed
Oui
Volume
9
Number
3
Pages
e0139521
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
antifungal resistance, antifungal susceptibility testing, candidiasis, thiosemicarbazone
Pubmed
Web of science
Open Access
Yes
Create date
08/11/2021 16:46
Last modification date
22/01/2022 7:32
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