Link to Pubmed [PMID] – 27855079
Epub ahead of print]
Horizontal gene transfer may occur between distantly related bacteria thus leading to genetic plasticity and in some cases to acquisition of novel resistance traits. Proteus mirabilis is an Enterobacterial species responsible for human infections that may express various acquired ß-lactam resistance genes, including different classes of carbapenemase genes. Here we report a Proteus mirabilis clinical isolate (1091) displaying resistance to penicillin, including temocillin, together with reduced susceptibility to carbapenems and susceptibility to expanded-spectrum cephalosporins. Using biochemical tests, significant carbapenem hydrolysis could be detected in P. mirabilis 1091. Since PCR failed to detect acquired carbapenemase genes commonly found in Enterobactericeae we used a whole genome sequencing approach that revealed the presence of blaOXA-58 class D carbapenemase gene, so far only identified in Acinetobacter sp.. This gene was located on a 3.1-kb element co-harboring a blaAmpC-like gene. Remarkably these two genes were bracketed by putative XerC-XerD binding sites and inserted at a XerC-XerD site located between the terminase-like small and large subunit genes of a bacteriophage. Increased expression of the two bla genes resulted from a 6-time tandem amplification of the element as revealed by Southern blotting. This is the first isolation of a clinical P. mirabilis strain producing OXA-58, a class D carbapenemase and the first description of a XerC-XerD dependent insertion of antibiotic resistance genes within a bacteriophage. This study revealed a new role for the XerC-XerD recombinase in bacteriophage biology.