The GPCR antagonist PPTN synergizes with caspofungin providing increased fungicidal activity against <i>Aspergillus fumigatus</i>

Invasive fungal infections have a high mortality rate, causing more deaths annually than tuberculosis or malaria. <i>Aspergillus fumigatus</i> is the main etiological agent of aspergillosis, one of the most prevalent and deadly fungal diseases. There are few therapeutic options for treating this disease, and treatment commonly fails due to host complications or the emergence of antifungal resistance. Drug repurposing, where existing drugs are deployed for other clinical indications, has increasingly been used in the process of drug discovery. Here, we show that 4-[4-(4-Piperidinyl) phenyl]-7-[4-(-(trifluoromethyl) phenyl]-2-naphthalenecarboxylic acid (PPTN), a highly specific antagonist of the human P2Y14 receptor, when combined with caspofungin (CAS), ibrexafungerp, voriconazole (VOR), and amphotericin can increase the fungicidal activity against not only <i>A. fumigatus</i> CAS- and VOR-resistant clinical isolates but also CAS against <i>Candida</i> spp.

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Publication Details

Journal
Microbiology Spectrum
Published
2025-03-17
DOI
https://doi.org/10.1128/spectrum.03318-24
Primary Topic
Antifungal resistance and susceptibility
Type
article
Field-Weighted Citation Impact
0.00

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article

The GPCR antagonist PPTN synergizes with caspofungin providing increased fungicidal activity against Aspergillus fumigatus

Thaila Fernanda dos Reis, Bradley Laflamme, Sara Fallah, Gustavo H. Goldman et al.
Microbiology Spectrum
Antifungal resistance and susceptibility
article

The GPCR antagonist PPTN synergizes with caspofungin providing increased fungicidal activity against Aspergillus fumigatus

Thaila Fernanda dos Reis, Bradley Laflamme, Sara Fallah, Gustavo H. Goldman, Endrews Delbaje, Leah E. Cowen, Camila Figueiredo Pinzan, Rafael Wesley Bastos, Suzanne Ackloo, Nicole Robbins
article en

Abstract

Invasive fungal infections have a high mortality rate, causing more deaths annually than tuberculosis or malaria. <i>Aspergillus fumigatus</i> is the main etiological agent of aspergillosis, one of the most prevalent and deadly fungal diseases. There are few therapeutic options for treating this disease, and treatment commonly fails due to host complications or the emergence of antifungal resistance. Drug repurposing, where existing drugs are deployed for other clinical indications, has increasingly been used in the process of drug discovery. Here, we show that 4-[4-(4-Piperidinyl) phenyl]-7-[4-(-(trifluoromethyl) phenyl]-2-naphthalenecarboxylic acid (PPTN), a highly specific antagonist of the human P2Y14 receptor, when combined with caspofungin (CAS), ibrexafungerp, voriconazole (VOR), and amphotericin can increase the fungicidal activity against not only <i>A. fumigatus</i> CAS- and VOR-resistant clinical isolates but also CAS against <i>Candida</i> spp.

Microbiology SpectrumVol. 13(5)
Universidade de São Paulo (BR), University of Toronto (CA), Structural Genomics Consortium (CA), Universidade Federal do Rio Grande do Norte (BR), National Institute of Science and Technology (ID)
Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, National Institute of Allergy and Infectious Diseases
Good health and well-being
Openalex Percentile: Top 93%
Antifungal resistance and susceptibility
DOIOpen Access PDFOpenAlex
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