<br>宿主防御肽模拟物 brilacidin 增强卡泊芬净针对人类病原真菌的抗真菌活性,Nature Communications

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宿主防御肽模拟物 brilacidin 增强卡泊芬净针对人类病原真菌的抗真菌活性
Nature Communications ( IF 14.7 ) Pub Date : 2023-04-12 , DOI: 10.1038/s41467-023-37573-y
Thaila Fernanda Dos Reis ₁ , Patrícia Alves de Castro ₁ , Rafael Wesley Bastos ₁ , Camila Figueiredo Pinzan ₁ , Pedro F N Souza ₂ , Suzanne Ackloo ₃ , Mohammad Anwar Hossain ₄ , David Harold Drewry _{4,

5} , Sondus Alkhazraji ₆ , Ashraf S Ibrahim _{6,

7} , Hyunil Jo ₈ , Jorge D Lightfoot ₉ , Emily M Adams ₉ , Kevin K Fuller _{9,

10} , William F deGrado ₈ , Gustavo H Goldman ₁

Affiliation

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Visiting professor at Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, 60451, Brazil.
Structural Genomics Consortium, University of Toronto, 101 College Street, MaRS South Tower, Suite 700, Toronto, ON, M5G 1L7, Canada.
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.
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.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94143, USA.
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.

真菌感染每年导致超过 150 万人死亡。由于新出现的抗真菌药物耐药性，迫切需要新的策略来对抗危及生命的真菌疾病。在这里，我们确定了宿主防御肽模拟物 brilacidin (BRI) 作为卡泊芬净 (CAS) 的增效剂，对抗 CAS 敏感和 CAS 耐药的烟曲霉、白色念珠菌、耳念珠菌和 CAS 本质耐药的新型隐球菌分离株。 BRI 还可以增强唑类药物对烟曲霉和几种毛霉目的真菌的作用。 BRI 通过影响细胞壁完整性途径和细胞膜电位在烟曲霉中发挥作用。 BRI 与 CAS 联合显着清除了免疫抑制的侵袭性肺曲霉病小鼠模型中的烟曲霉肺部感染。单独使用 BRI 还可降低真菌性角膜炎小鼠模型中的烟曲霉真菌负荷并消除疾病发展。我们的结果表明，临床使用中 BRI 和抗真菌药物的组合可能会改善曲霉病和其他真菌感染的治疗结果。

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更新日期：2023-04-12

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