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Humans and animals are ubiquitously colonized by Enterobacteriaceae , including both commensals and clinically significant pathogens. Here, we report 21 complete Enterobacteriaceae megaplasmid genomes of up to 1.58 Mbp in length spanning two major clades that are highly divergent from previously described plasmids. Of these, three were reconstructed from isolates of Escherichia coli and Shigella flexneri ; others were potentially hosted by species of Citrobacter and Enterobacter . Related megabase-scale plasmids were detected in at least 400 infant and adult gut, and other microbiomes. Diverse Enterobacteriaceae hosts, conjugation machinery, and DNA modification patterns suggest that these elements are self-transmissible, with a broad host range. The plasmids encode multi-drug efflux systems and potential secreted effectors. Up to 208 tRNAs are encoded and include sequence variants that may counter tRNA-centric defense mechanisms. Overall, the vast plasmid coding capacity may broaden host range, increase competitiveness, control invasion by other elements, and counter programmed cell death.
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Guitor et al. (2026) studied this question.
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