Abstract
AbstractThe causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism within the phylumBacteroidotaremain unclear (1, 2). Using the classical lipopolysaccharide/O-antigen ‘rfboperon’ inEnterobacteriaceaeas a surface antigen model (5-gene-clusterrfbABCDX), and a recentrfbA-typing strategy for strain classification (3), we characterized the architecture/conservancy of the entirerfboperon inBacteroidota. Analyzing complete genomes, we discovered that mostBacteroidotahave therfboperon 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 predominantlyBacteroides-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 whyBacteroidotahave 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/CavFTBacteroidotastimulate macrophages with lower potency thanEnterobacteriaceae, 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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