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A small molecule produced by Lactobacillus species blocks Candida albicans filamentation by inhibiting a DYRK1-family kinase.
MacAlpine, Jessie; Daniel-Ivad, Martin; Liu, Zhongle; Yano, Junko; Revie, Nicole M; Todd, Robert T; Stogios, Peter J; Sanchez, Hiram; O'Meara, Teresa R; Tompkins, Thomas A; Savchenko, Alexei; Selmecki, Anna; Veri, Amanda O; Andes, David R; Fidel, Paul L; Robbins, Nicole; Nodwell, Justin; Whitesell, Luke; Cowen, Leah E.
Afiliación
  • MacAlpine J; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • Daniel-Ivad M; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
  • Liu Z; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • Yano J; Center of Excellence in Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, LA, USA.
  • Revie NM; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • Todd RT; Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
  • Stogios PJ; BioZone, Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
  • Sanchez H; Center for Structural Genomics of Infectious Diseases (CSGID), Chicago, IL, USA.
  • O'Meara TR; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
  • Tompkins TA; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI, USA.
  • Savchenko A; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
  • Selmecki A; Rosell Institute for Microbiome and Probiotics, 6100 Avenue Royalmount, Montreal, QC, Canada.
  • Veri AO; BioZone, Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada.
  • Andes DR; Center for Structural Genomics of Infectious Diseases (CSGID), Chicago, IL, USA.
  • Fidel PL; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada.
  • Robbins N; Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
  • Nodwell J; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • Whitesell L; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
  • Cowen LE; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI, USA.
Nat Commun ; 12(1): 6151, 2021 10 22.
Article en En | MEDLINE | ID: mdl-34686660
The fungus Candida albicans is an opportunistic pathogen that can exploit imbalances in microbiome composition to invade its human host, causing pathologies ranging from vaginal candidiasis to fungal sepsis. Bacteria of the genus Lactobacillus are colonizers of human mucosa and can produce compounds with bioactivity against C. albicans. Here, we show that some Lactobacillus species produce a small molecule under laboratory conditions that blocks the C. albicans yeast-to-filament transition, an important virulence trait. It remains unexplored whether the compound is produced in the context of the human host. Bioassay-guided fractionation of Lactobacillus-conditioned medium linked this activity to 1-acetyl-ß-carboline (1-ABC). We use genetic approaches to show that filamentation inhibition by 1-ABC requires Yak1, a DYRK1-family kinase. Additional biochemical characterization of structurally related 1-ethoxycarbonyl-ß-carboline confirms that it inhibits Yak1 and blocks C. albicans biofilm formation. Thus, our findings reveal Lactobacillus-produced 1-ABC can prevent the yeast-to-filament transition in C. albicans through inhibition of Yak1.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Tirosina Quinasas / Candida albicans / Proteínas Serina-Treonina Quinasas / Inhibidores de Proteínas Quinasas / Lactobacillus / Antifúngicos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Tirosina Quinasas / Candida albicans / Proteínas Serina-Treonina Quinasas / Inhibidores de Proteínas Quinasas / Lactobacillus / Antifúngicos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido