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Bacillamide D produced by Bacillus cereus from the mouse intestinal bacterial collection (miBC) is a potent cytotoxin in vitro.
Hohmann, Maximilian; Brunner, Valentina; Johannes, Widya; Schum, Dominik; Carroll, Laura M; Liu, Tianzhe; Sasaki, Daisuke; Bosch, Johanna; Clavel, Thomas; Sieber, Stephan A; Zeller, Georg; Tschurtschenthaler, Markus; Janßen, Klaus-Peter; Gulder, Tobias A M.
Afiliación
  • Hohmann M; Chair of Technical Biochemistry, Technical University of Dresden, Bergstraße 66, 01069, Dresden, Germany.
  • Brunner V; Chair of Translational Cancer Research and Institute of Experimental Cancer Therapy, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, 81675, Munich, Germany.
  • Johannes W; Center for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, 81675, Munich, Germany.
  • Schum D; Division of Translational Cancer Research German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120, Heidelberg, Germany.
  • Carroll LM; Department of Surgery, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, 81675, Munich, Germany.
  • Liu T; Department of Bioscience, Center for Functional Protein Assemblies, Technical University of Munich, 85748, Garching bei München, Germany.
  • Sasaki D; Structural and Computational Biology Unit, European Molecular Biology Laboratory, 61997, Heidelberg, Germany.
  • Bosch J; Chair of Technical Biochemistry, Technical University of Dresden, Bergstraße 66, 01069, Dresden, Germany.
  • Clavel T; Department of Surgery, Klinikum rechts der Isar, School of Medicine and Health, Technical University of Munich, 81675, Munich, Germany.
  • Sieber SA; Research and Development Headquarters, Nitto Boseki Co., Ltd., 102-8489, Tokyo, Japan.
  • Zeller G; Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, 52074, Aachen, Germany.
  • Tschurtschenthaler M; Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, 52074, Aachen, Germany.
  • Janßen KP; Department of Bioscience, Center for Functional Protein Assemblies, Technical University of Munich, 85748, Garching bei München, Germany.
  • Gulder TAM; Structural and Computational Biology Unit, European Molecular Biology Laboratory, 61997, Heidelberg, Germany.
Commun Biol ; 7(1): 655, 2024 May 28.
Article en En | MEDLINE | ID: mdl-38806706
ABSTRACT
The gut microbiota influences human health and the development of chronic diseases. However, our understanding of potentially protective or harmful microbe-host interactions at the molecular level is still in its infancy. To gain further insights into the hidden gut metabolome and its impact, we identified a cryptic non-ribosomal peptide BGC in the genome of Bacillus cereus DSM 28590 from the mouse intestine ( www.dsmz.de/miBC ), which was predicted to encode a thiazol(in)e substructure. Cloning and heterologous expression of this BGC revealed that it produces bacillamide D. In-depth functional evaluation showed potent cytotoxicity and inhibition of cell migration using the human cell lines HCT116 and HEK293, which was validated using primary mouse organoids. This work establishes the bacillamides as selective cytotoxins from a bacterial gut isolate that affect mammalian cells. Our targeted structure-function-predictive approach is demonstrated to be a streamlined method to discover deleterious gut microbial metabolites with potential effects on human health.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacillus cereus / Microbioma Gastrointestinal Límite: Animals / Humans Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacillus cereus / Microbioma Gastrointestinal Límite: Animals / Humans Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido