دورية أكاديمية
أعرض في EDS

A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.

التفاصيل البيبلوغرافية
العنوان: A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.
المؤلفون: 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.; Lineberger Comprehensive Cancer Center, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Alkhazraji S; Division of Infectious Diseases, The Lundquist Institute for Biomedical Innovation at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, 90502, 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.; David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA., Jo H; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94143, USA., Lightfoot JD; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA., Adams EM; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA., Fuller KK; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA., deGrado WF; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94143, USA., Goldman GH; Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. ggoldman@usp.br.
المصدر: Nature communications [Nat Commun] 2023 Apr 12; Vol. 14 (1), pp. 2052. Date of Electronic Publication: 2023 Apr 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Aspergillosis*/microbiology , Mycoses*/drug therapy, Humans ; Mice ; Animals ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Caspofungin/pharmacology ; Caspofungin/therapeutic use ; Antimicrobial Cationic Peptides/therapeutic use ; Disease Models, Animal ; Aspergillus fumigatus ; Candida albicans ; Drug Resistance, Fungal
مستخلص: 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.
(© 2023. The Author(s).)
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معلومات مُعتمدة: P30 EY021725 United States EY NEI NIH HHS; R01 AI153356 United States AI NIAID NIH HHS; T32 EY023202 United States EY NEI NIH HHS; R01 AI063503 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Antifungal Agents)
F0XDI6ZL63 (Caspofungin)
I1679X069H (brilacidin)
0 (Antimicrobial Cationic Peptides)
تواريخ الأحداث: Date Created: 20230412 Date Completed: 20230414 Latest Revision: 20240106
رمز التحديث: 20240106
مُعرف محوري في PubMed: PMC10090755
DOI: 10.1038/s41467-023-37573-y
PMID: 37045836
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-37573-y