A genetic system for Akkermansia muciniphila reveals a role for mucin foraging in gut colonization and host sterol biosynthesis gene expression.

Autor: Davey LE; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA. laurendavey@uvic.ca.; Duke Microbiome Center, Duke University, Durham, NC, USA. laurendavey@uvic.ca.; Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada. laurendavey@uvic.ca., Malkus PN; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.; Duke Microbiome Center, Duke University, Durham, NC, USA., Villa M; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.; Duke Microbiome Center, Duke University, Durham, NC, USA., Dolat L; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.; Duke Microbiome Center, Duke University, Durham, NC, USA., Holmes ZC; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.; Duke Microbiome Center, Duke University, Durham, NC, USA., Letourneau J; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.; Duke Microbiome Center, Duke University, Durham, NC, USA., Ansaldo E; Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., David LA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.; Duke Microbiome Center, Duke University, Durham, NC, USA., Barton GM; Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Valdivia RH; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA. raphael.valdivia@duke.edu.; Duke Microbiome Center, Duke University, Durham, NC, USA. raphael.valdivia@duke.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2023 Aug; Vol. 8 (8), pp. 1450-1467. Date of Electronic Publication: 2023 Jun 19.
DOI: 10.1038/s41564-023-01407-w
Abstrakt: Akkermansia muciniphila, a mucophilic member of the gut microbiota, protects its host against metabolic disorders. Because it is genetically intractable, the mechanisms underlying mucin metabolism, gut colonization and its impact on host physiology are not well understood. Here we developed and applied transposon mutagenesis to identify genes important for intestinal colonization and for the use of mucin. An analysis of transposon mutants indicated that de novo biosynthesis of amino acids was required for A. muciniphila growth on mucin medium and that many glycoside hydrolases are redundant. We observed that mucin degradation products accumulate in internal compartments within bacteria in a process that requires genes encoding pili and a periplasmic protein complex, which we term mucin utilization locus (MUL) genes. We determined that MUL genes were required for intestinal colonization in mice but only when competing with other microbes. In germ-free mice, MUL genes were required for A. muciniphila to repress genes important for cholesterol biosynthesis in the colon. Our genetic system for A. muciniphila provides an important tool with which to uncover molecular links between the metabolism of mucins, regulation of lipid homeostasis and potential probiotic activities.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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