The tet39 Determinant and the msrE-mphE Genes in Acinetobacter Plasmids Are Each Part of Discrete Modules Flanked by Inversely Oriented p dif (XerC-XerD) Sites

Thetet39 tetracycline resistance determinant and the macrolide resistance genesmsrE andmphE were found in an 18.2-kb plasmid, pS30-1, recovered from a global clone 2 (GC2)Acinetobacter baumannii isolate from Singapore, that conferred resistance to tetracycline and erythromycin. pS30-1 also containsmobA andmobC genes encoding MOBQ family proteins, but attempts to mobilize pS30-1 utilizing a coresident conjugativerepAci6 plasmid were unsuccessful. Eight pdif sites, consisting of inversely oriented binding sites for the XerC and XerD recombinases separated by 6 bp, were detected in pS30-1. Thetet39 determinant and themsrE-mphE gene pair are each surrounded by two pdif sites in inverse orientation. Identical regions in different contexts and many previously unnoticed pdif sites were found in a number of different plasmids in GenBank, showing that thetet39 andmsrE-mphE dif modules are mobile. A putative toxin/antitoxin system, a gene encoding a serine recombinase, and open reading frames of unknown function were also part ofdif modules in pS30-1. In general, modules with internal XerC or XerD sites alternate. Two copies of ISAjo2-1 (94% identical to ISAjo2 ) in pS30-1 were inserted 5 bp from a XerC site, and this appears to be the preferred insertion site for this insertion sequence (IS) group. Apparently,Acinetobacter plasmids exploit theAcinetobacter XerC-XerD recombinases to mobilize DNA units containing resistance and other genes, via an uncharacterized mechanism. Thetet39 andmsrE-mphE dif modules add to theoxa24 module and theoxa58 module redefined here, bringing the total of resistance gene-containingdif modules inAcinetobacter plasmids to four.