Host range of strand-biased circularizing integrative elements: a new class of mobile DNA elements nesting in Gammaproteobacteria

Abstract BackgroundThe strand-biased circularizing integrative elements (SEs) are putatively non-mobilizable integrative elements for transmitting antimicrobial resistance genes. However, the prevalence of SEs in prokaryotes remains unclear. To address this, the SE core genes were defined based on the gene knockout experiments as well as conservation level, and then the synteny blocks of their distant homologs were searched in the RefSeq complete genome sequence database using PSI-BLAST.ResultsAt least three conserved coding sequences (intA, intB, srap) were identified as essential for SE circularization. One conserved coding sequences (tfp) could not be deleted. The synteny blocks of tfp and srap homologs were detected in 3.6% of the replicons of Gammaproteobacteria but not in the other taxa, implying that the SE movement is host-dependent. SEs have been discovered most frequently in the order Vibrionales (18% of replicons), Pseudomonadales (18%), Alteromonadales (17%), and Aeromonadales (12%). Genome comparisons revealed 35 new SE members with identifiable termini. SEs are present at 1 to 2 copies per replicon and are 15.7 kb long in the median. Three newly identified SE members carry antimicrobial resistance genes, like tmexCD-toprJ, mcr-9, and blaVHH. Further experiments validated that three new SE members possess strand-biased copy-out activity.ConclusionsThis study identified three SE core genes essential for SE circularization. The main hosts of SEs are a subset of free-living Gammaproteobacteria, which are rather narrow among the usual host range of mobile DNA element families discovered to date. As the host range, genetic organization, and movements are unique among the mobile DNA elements, SE and its distant relative, GInt, provide a new model system for the host-mobile DNA element coevolution studies.