ABSTRACT
A multidrug-resistant Klebsiella pneumoniae 1210 isolate with reduced carbapenem susceptibility revealed the presence of a novel plasmid-encoded blaOXA-48-like gene, named blaOXA-519 The 60.7-kb plasmid (pOXA-519) was similar to the IncL-OXA-48 prototypical plasmid except for a ca. 2-kb deletion due to an IS1R insertion. OXA-519 differed from OXA-48 by a Val120Leu substitution, which resulted in an overall reduced ß-lactam-hydrolysis profile, except those for ertapenem and meropenem, which were increased. Thus, detection of OXA-519 producers using biochemical tests that monitor imipenem hydrolysis will be difficult.
Subject(s)
Base Sequence , Klebsiella pneumoniae/genetics , Mutagenesis, Insertional , Plasmids/chemistry , Sequence Deletion , beta-Lactam Resistance/genetics , beta-Lactamases/genetics , Aged, 80 and over , Amino Acid Substitution , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Ertapenem/metabolism , Ertapenem/pharmacology , Humans , Hydrolysis , Imipenem/metabolism , Imipenem/pharmacology , Isoenzymes/genetics , Isoenzymes/metabolism , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , Klebsiella pneumoniae/isolation & purification , Meropenem/metabolism , Meropenem/pharmacology , Microbial Sensitivity Tests , Plasmids/metabolism , beta-Lactamases/metabolismABSTRACT
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 (strain 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 was detected in P. mirabilis 1091. Since PCR failed to detect acquired carbapenemase genes commonly found in Enterobacteriaceae, we used a whole-genome sequencing approach that revealed the presence of blaOXA-58 class D carbapenemase gene, so far identified only in Acinetobacter species. This gene was located on a 3.1-kb element coharboring 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.
