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An oxylipin signal confers protection against antifungal echinocandins in pathogenic aspergilli.
Calise, Dante G; Park, Sung Chul; Bok, Jin Woo; Goldman, Gustavo H; Keller, Nancy P.
Afiliación
  • Calise DG; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
  • Park SC; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, USA.
  • Bok JW; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
  • Goldman GH; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
  • Keller NP; Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Nat Commun ; 15(1): 3770, 2024 May 04.
Article en En | MEDLINE | ID: mdl-38704366
ABSTRACT
Aspergillus fumigatus is the leading causative agent of life-threatening invasive aspergillosis in immunocompromised individuals. One antifungal class used to treat Aspergillus infections is the fungistatic echinocandins, semisynthetic drugs derived from naturally occurring fungal lipopeptides. By inhibiting beta-1,3-glucan synthesis, echinocandins cause both fungistatic stunting of hyphal growth and repeated fungicidal lysis of apical tip compartments. Here, we uncover an endogenous mechanism of echinocandin tolerance in A. fumigatus whereby the inducible oxylipin signal 5,8-diHODE confers protection against tip lysis via the transcription factor ZfpA. Treatment of A. fumigatus with echinocandins induces 5,8-diHODE synthesis by the fungal oxygenase PpoA in a ZfpA dependent manner resulting in a positive feedback loop. This protective 5,8-diHODE/ZfpA signaling relay is conserved among diverse isolates of A. fumigatus and in two other Aspergillus pathogens. Our findings reveal an oxylipin-directed growth program-possibly arisen through natural encounters with native echinocandin producing fungi-that enables echinocandin tolerance in pathogenic aspergilli.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aspergilosis / Aspergillus fumigatus / Proteínas Fúngicas / Oxilipinas / Equinocandinas / Antifúngicos Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aspergilosis / Aspergillus fumigatus / Proteínas Fúngicas / Oxilipinas / Equinocandinas / Antifúngicos Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido