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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number695240
JournalFrontiers in Cellular and Infection Microbiology
Volume11
DOIs
StatePublished - Jun 23 2021

Bibliographical note

Funding Information:
This study was supported by Appili Therapeutics, Inc. research award CON000000083519. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Additional funding to support the collection and analysis of the clinical isolates was supported by NIH grants U01AI089244 and R01NS086312 to DB and R01NS118538 to KN.

Funding Information:
Conflict of Interest: KN received funding from Appili Therapeutics Inc.

Publisher Copyright:
© Copyright © 2021 Gerlach, Altamirano, Yoder, Luggya, Akampurira, Meya, Boulware, Rhein and Nielsen.

Keywords

  • ATI-2307
  • Cryptococcus
  • IC
  • T-2307
  • antifungal
  • azole
  • resistance
  • susceptibility

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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