Bacillamide D produced by Bacillus cereus from the mouse intestinal bacterial collection (miBC) is a potent cytotoxin in vitro.

Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE

Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-

Bacillus cereus*/metabolism ; Bacillus cereus*/genetics ; Gastrointestinal Microbiome*; Animals ; Mice ; Humans ; HEK293 Cells ; Cytotoxins/metabolism ; Cytotoxins/genetics ; HCT116 Cells ; Intestines/microbiology ; Cell Movement ; Organoids/metabolism

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.
(© 2024. The Author(s).)

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SFB 1371 Deutsche Forschungsgemeinschaft (German Research Foundation); INST 269/971-1 Deutsche Forschungsgemeinschaft (German Research Foundation)

0 (Cytotoxins)

Date Created: 20240528 Date Completed: 20240528 Latest Revision: 20241216

20241217

PMC11133360

10.1038/s42003-024-06208-3

38806706