A Genomic Toolkit for the Mechanistic Dissection of Intractable Human Gut Bacteria.

Autor: Bisanz JE; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Soto-Perez P; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Noecker C; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Aksenov AA; Collaborative Mass Spectrometry Innovation Center, Department of Pediatrics, Center for Microbiome Innovation, Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA 92093, USA., Lam KN; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Kenney GE; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA., Bess EN; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Haiser HJ; Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA., Kyaw TS; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Yu FB; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA., Rekdal VM; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA., Ha CWY; Department of Medicine, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Devkota S; Department of Medicine, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Balskus EP; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA., Dorrestein PC; Collaborative Mass Spectrometry Innovation Center, Department of Pediatrics, Center for Microbiome Innovation, Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA 92093, USA., Allen-Vercoe E; Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada., Turnbaugh PJ; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: peter.turnbaugh@ucsf.edu.
Jazyk: angličtina
Zdroj: Cell host & microbe [Cell Host Microbe] 2020 Jun 10; Vol. 27 (6), pp. 1001-1013.e9. Date of Electronic Publication: 2020 Apr 28.
DOI: 10.1016/j.chom.2020.04.006
Abstrakt: Despite the remarkable microbial diversity found within humans, our ability to link genes to phenotypes is based upon a handful of model microorganisms. We report a comparative genomics platform for Eggerthella lenta and other Coriobacteriia, a neglected taxon broadly relevant to human health and disease. We uncover extensive genetic and metabolic diversity and validate a tool for mapping phenotypes to genes and sequence variants. We also present a tool for the quantification of strains from metagenomic sequencing data, enabling the identification of genes that predict bacterial fitness. Competitive growth is reproducible under laboratory conditions and attributable to intrinsic growth rates and resource utilization. Unique signatures of in vivo competition in gnotobiotic mice include an adhesin enriched in poor colonizers. Together, these computational and experimental resources represent a strong foundation for the continued mechanistic dissection of the Coriobacteriia and a template that can be applied to study other genetically intractable taxa.
Competing Interests: Declaration of Interests P.J.T. is on the scientific advisory boards for Kaleido, Pendulum, Seres, and SNIPRbiome. E.A.V. is co-founder and CSO of NuBiyota. All other authors declare no competing interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE