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. 2021 Jun 23:11:695240.
doi: 10.3389/fcimb.2021.695240. eCollection 2021.

ATI-2307 Exhibits Equivalent Antifungal Activity in Cryptococcus neoformans Clinical Isolates With High and Low Fluconazole IC50

Elliot S Gerlach  1 , Sophie Altamirano  1 , J Marina Yoder  1 , Tony S Luggya  2 , Andrew Akampurira  2 , David B Meya  2 , David R Boulware  3 , Joshua Rhein  3 , Kirsten Nielsen  1
Affiliations

ATI-2307 Exhibits Equivalent Antifungal Activity in Cryptococcus neoformans Clinical Isolates With High and Low Fluconazole IC50

Elliot S Gerlach et al. Front Cell Infect Microbiol. .

Abstract

Half maximal inhibitory concentrations (IC50) to the experimental drug ATI-2307 and complete inhibition (IC90) of the common clinically used antifungal drug amphotericin B were determined by microbroth dilution assay for a collection of 69 clinical isolates of Cryptococcus neoformans from Uganda that had high fluconazole IC50 values. The majority of the clinical isolates tested had fluconazole IC50 at or above 8 µg/mL, but were susceptible to both amphotericin B (IC90 ≤1 μg/mL) and ATI-2307 (IC50 ≤0.0312 µg/mL). No correlation between increased fluconazole minimum inhibitory concentration (MIC) and ATI-2307 or amphotericin B MIC was observed, suggesting that the cellular changes impacting fluconazole susceptibility did not impact the effectiveness of ATI-2307. Our results suggest that ATI-2307 is a promising new antifungal drug for use in the context of high fluconazole or other antifungal drug MICs and/or in combination drug therapy regimens.

Keywords: ATI-2307; Cryptococcus; IC50; T-2307; antifungal; azole; resistance; susceptibility.

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Conflict of interest statement

KN received funding from Appili Therapeutics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Correlation between fluconazole IC50, amphotericin B IC90, and ATI-2307 IC50 values for Cryptococcus neoformans clinical isolates. No correlation was observed between (A) fluconazole and amphotericin B susceptibilities (rho = 0.2049, P = 0.21), (B) fluconazole and ATI-2307 susceptibilities (rho = -0.1690, P = 0.1650), or (C) amphotericin B and ATI-2307 susceptibilities (rho = 0.0125, P = 0.9190).
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