Acquisition of MACPF domain-encoding genes is the main contributor to LPS glycan diversity in gut Bacteroides species


The ability to antagonize competing strains and species is often important for bacterial fitness in microbial communities. The extent to which intra-species antagonism drives phenotypic diversity of bacterial species is rarely examined in a comprehensive manner at both the genetic and phenotypic levels. Here we show that for nine abundant human gut Bacteroides species examined, there are only a few LPS glycan genetic types. We show that for a given Bacteroides species, there is a predominant lipopolysaccharide (LPS) glycan locus present in the majority of strains. However, other strains have replacements of glycosyltransferase-encoding genes, in most cases, adjacent to a membrane attack/perforin (MACPF) domain-encoding gene not present in the predominant type. We show that the MACPF genes present in LPS glycan biosynthesis loci of four Bacteroides species encode antimicrobial proteins and in Bacteroides vulgatus and Bacteroides dorei, we show the MACPF toxin targets the LPS of strains with the predominant LPS glycan locus. By a combination of gene deletion and replacement, we converted a MACPF toxin-producing strain into a sensitive strain. Genetic diversity of LPS glycan biosynthesis regions in Bacteroides is similar to phage serotype conversion whereby the receptor is altered to render the strain immune to infection/toxicity, and is a rare example in bacteria of toxin immunity conferred to the toxin-producing strain by replacement of genetic material to modify the receptor rather than by a cognate immunity protein.

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This work was supported by Public Health Service grant R01AI093771 from the NIH/National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. B. (thetaiotaomicron) 1_1_6, B. (dorei) 9_1_42FAA, B. (dorei) 5_1_36/D4, and B. fragilis 2_1_16, were obtained through BEI Resources as part of the Human Microbiome Project. We thank Kevin Roelofs and Leonor GarciaBayona for helpful discussions.

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Correspondence to Laurie E. Comstock.

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