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A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.
Dos Reis, Thaila Fernanda; de Castro, Patrícia Alves; Bastos, Rafael Wesley; Pinzan, Camila Figueiredo; Souza, Pedro F N; Ackloo, Suzanne; Hossain, Mohammad Anwar; Drewry, David Harold; Alkhazraji, Sondus; Ibrahim, Ashraf S; Jo, Hyunil; Lightfoot, Jorge D; Adams, Emily M; Fuller, Kevin K; deGrado, William F; Goldman, Gustavo H.
Afiliación
  • Dos Reis TF; Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • de Castro PA; Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Bastos RW; Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Pinzan CF; Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Souza PFN; Visiting professor at Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, 60451, Brazil.
  • Ackloo S; Structural Genomics Consortium, University of Toronto, 101 College Street, MaRS South Tower, Suite 700, Toronto, ON, M5G 1L7, Canada.
  • Hossain MA; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Drewry DH; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Alkhazraji S; Lineberger Comprehensive Cancer Center, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Ibrahim AS; Division of Infectious Diseases, The Lundquist Institute for Biomedical Innovation at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, 90502, USA.
  • Jo H; Division of Infectious Diseases, The Lundquist Institute for Biomedical Innovation at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, 90502, USA.
  • Lightfoot JD; David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
  • Adams EM; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94143, USA.
  • Fuller KK; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
  • deGrado WF; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
  • Goldman GH; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Nat Commun ; 14(1): 2052, 2023 04 12.
Article en En | MEDLINE | ID: mdl-37045836
ABSTRACT
Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, we identify the host defense peptide mimetic, brilacidin (BRI) as a synergizer with caspofungin (CAS) against CAS-sensitive and CAS-resistant isolates of Aspergillus fumigatus, Candida albicans, C. auris, and CAS-intrinsically resistant Cryptococcus neoformans. BRI also potentiates azoles against A. fumigatus and several Mucorales fungi. BRI acts in A. fumigatus by affecting cell wall integrity pathway and cell membrane potential. BRI combined with CAS significantly clears A. fumigatus lung infection in an immunosuppressed murine model of invasive pulmonary aspergillosis. BRI alone also decreases A. fumigatus fungal burden and ablates disease development in a murine model of fungal keratitis. Our results indicate that combinations of BRI and antifungal drugs in clinical use are likely to improve the treatment outcome of aspergillosis and other fungal infections.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Aspergilosis / Micosis Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Brasil
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Aspergilosis / Micosis Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Brasil