The tet39 determinant and the msrE-mphE genes in Acinetobacter plasmids are each part of discrete modules flanked by inversely-oriented pdif (XerC-XerD) sites [PublishAheadOfPrint]

The tet39 tetracycline resistance determinant and the macrolide resistance genes msrE and mphE were found in an 18.2 kb plasmid, pS30-1, recovered from a GC2 Acinetobacter baumannii isolate from Singapore, that conferred resistance to tetracycline and erythromycin. pS30-1 also contains mobA and mobC genes encoding MOB_Q family proteins but attempts to mobilise pS30-1 utilising a co-resident conjugative repAci6 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. The tet39 determinant and the msrE-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 the tet39 and msrE-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 of dif 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 IS group. Apparently, Acinetobacter plasmids exploit the Acinetobacter XerC-XerD recombinases to mobilise DNA units containing resistance and other genes, via an uncharacterised mechanism. The tet39 and msrE-mphE dif modules add to the oxa24 module and the oxa58 module redefined here, bringing the total resistance-gene-containing dif modules in Acinetobacter plasmids to four.

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