A subclass of the IS1202family of bacterial insertion sequences targets XerCD recombination sites

AbstractIS1202, originally isolated fromStreptococcus pneumoniain the mid-1990s had been previously tagged as an emerging IS family in ISfinder. While searching for plasmid-associated Xer recombinase recombination sites (xrs) inAcinetobacter baumannii, we observed that some insertion sequences related to IS1202were repeatedly found abutting these sites in a number of plasmids. The plasmids often carried repeatedxrsthought to form a new type of mobile genetic element (MGE) which uses the chromosomally-encoded XerCD recombinase for mobility. The MGE (xrscassette) consist ofxrsflanking one or a small number of genes often including different clinically important carbapenemase-encodingbla-OXA. The IS1202-related IS are inserted with their left, transposase proximal extremity, IRL, five base pairs fromxrsand include a characteristic 5bp flanking target duplication. Further searches revealed that many different plasmid- and chromosome-bornexrscan be targeted and that IS1202-xrscombinations are not limited toAcinetobacter baumanniibut occur in other bacteria.In addition to 28 IS1202group ISs in ISfinder and a number which had been subsequently submitted, we undertook a survey of the NCBI (February 2020) and identified 138 additional IS1202-related IS. These could be divided into 3 principal subgroups based on their transposase sequences and on the length of the DR generated on insertion: subgroup IS120227-28bp DR); ISTde1(15-17bp); and ISAba32(5-6bp). Members of each group which lacked DR were also found. But since other examples of most of these were subsequently identified having DR, those lacking DR may have been generated by intra-replicon recombination. Only members of the group which generate 5bp DR were found to targetxrs. These were not only identified in plasmids but also occurred at some individualxrssites,dif, located at the chromosome replication terminus and involved in post-replication chromosome segregation. Further analysis showed the presence of subgroup-specific indels in their transposases which may be responsible for the differences in their behavior.We propose that this collection of IS be classed as a new insertion sequence family: the IS1202family composed of at three subfamilies, only one of which specifically targets plasmid-bornexrs. We discuss the implications ofxrstargeting for gene mobility.