The basis of antigenic operon fragmentation in Bacteroidota and commensalism.

Autor:	Bank NC; Division of Gastroenterology and Liver Disease, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Singh V; Division of Gastroenterology and Liver Disease, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Grubb B; Division of Gastroenterology and Liver Disease, Case Western Reserve University School of Medicine, Cleveland, OH, USA., McCourt B; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Burberry A; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Roberts KD; Division of Gastroenterology and Liver Disease, Case Western Reserve University School of Medicine, Cleveland, OH, USA.; Germ-Free and Gut Microbiome Core, Case Western Reserve University, Cleveland, OH, USA., Rodriguez-Palacios A; Division of Gastroenterology and Liver Disease, Case Western Reserve University School of Medicine, Cleveland, OH, USA.; Digestive Health Research Institute, Case Western Reserve University School of Medicine, USA.; University Hospitals Research and Education Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.; Germ-Free and Gut Microbiome Core, Case Western Reserve University, Cleveland, OH, USA.; Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 02. Date of Electronic Publication: 2023 Jun 02.
DOI:	10.1101/2023.06.02.543472
Abstrakt:	The causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism within the phylum Bacteroidota remain unclear (1, 2). Using the classical lipopolysaccharide/O-antigen ' rfb operon' in Enterobacteriaceae as a surface antigen model (5-gene-cluster rfbABCDX ), and a recent rfbA- typing strategy for strain classification (3), we characterized the architecture/conservancy of the entire rfb operon in Bacteroidota . Analyzing complete genomes, we discovered that most Bacteroidota have the rfb operon fragmented into non-random gene-singlets and/or doublets/triplets, termed 'minioperons'. To reflect global operon integrity, duplication, and fragmentation principles, we propose a five-category (infra/supernumerary) cataloguing system and a Global Operon Profiling System for bacteria. Mechanistically, genomic sequence analyses revealed that operon fragmentation is driven by intra-operon insertions of predominantly Bacteroides -DNA ( thetaiotaomicron/fragilis ) and likely natural selection in specific micro-niches. Bacteroides -insertions, also detected in other antigenic operons (fimbriae), but not in operons deemed essential (ribosomal), could explain why Bacteroidota have fewer KEGG-pathways despite large genomes (4). DNA insertions overrepresenting DNA-exchange-avid species, impact functional metagenomics by inflating gene-based pathway inference and overestimating 'extra-species' abundance. Using bacteria from inflammatory gut-wall cavernous micro-tracts (CavFT) in Crohn's Disease (5), we illustrate that bacteria with supernumerary-fragmented operons cannot produce O-antigen, and that commensal/CavFT Bacteroidota stimulate macrophages with lower potency than Enterobacteriaceae , and do not induce peritonitis in mice. The impact of 'foreign-DNA' insertions on pro-inflammatory operons, metagenomics, and commensalism offers potential for novel diagnostics and therapeutics. Competing Interests: Conflict of Interest: The authors declare they have no conflicts of interest.
Databáze:	MEDLINE
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