Dataset Information

Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniae ST258.

ABSTRACT: BACKGROUND:OXA-2 is a class D ?-lactamase that confers resistance to penicillins, as well as narrow-spectrum cephalosporins. OXA-2 was recently reported to also possess carbapenem-hydrolysing activity. Here, we describe a KPC-2-encoding Klebsiella pneumoniae isolate that demonstrated reduced susceptibility to ceftazidime and ertapenem due to production of OXA-2. OBJECTIVES:To elucidate the role of OXA-2 production in reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 clinical isolate. METHODS:MICs were determined by the agar dilution method. WGS was conducted to identify and compare resistance genes between isolates. Expression of KPC-2 was quantified by quantitative RT-PCR and immunoblotting. OXA-2 was expressed in Escherichia coli TOP10, as well as in K. pneumoniae ATCC 13883, to define the relative contribution of OXA-2 in ?-lactam resistance. Kinetic studies were conducted using purified OXA-2 enzyme. RESULTS:K. pneumoniae 1761 belonged to ST258 and carried both blaKPC-2 and blaOXA-2. However, expression of blaKPC-2 was substantially reduced due to an IS1294 insertion in the promoter region. K. pneumoniae 1761, K. pneumoniae ATCC 13883 and E. coli TOP10 carrying blaOXA-2-harbouring plasmids showed reduced susceptibility to ertapenem and ceftazidime, but meropenem, imipenem and cefepime were unaffected. blaOXA-2 was carried on a 2910?bp partial class 1 integron containing aacA4-blaOXA-2-qacE?1-sul1 on an IncA/C2 plasmid, which was not present in the earlier ST258 isolates possessing blaKPC-2 with intact promoters. Hydrolysis of ertapenem by OXA-2 was confirmed using purified enzyme. CONCLUSIONS:Production of OXA-2 was associated with reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 isolate.

SUBMITTER: Iovleva A

PROVIDER: S-EPMC6640307 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniae ST258.

Iovleva Alina A Mettus Roberta T RT McElheny Christi L CL Mustapha Mustapha M MM Van Tyne Daria D Shields Ryan K RK Pasculle A William AW Cooper Vaughn S VS Doi Yohei Y

The Journal of antimicrobial chemotherapy 20190801 8

<h4>Background</h4>OXA-2 is a class D β-lactamase that confers resistance to penicillins, as well as narrow-spectrum cephalosporins. OXA-2 was recently reported to also possess carbapenem-hydrolysing activity. Here, we describe a KPC-2-encoding Klebsiella pneumoniae isolate that demonstrated reduced susceptibility to ceftazidime and ertapenem due to production of OXA-2.<h4>Objectives</h4>To elucidate the role of OXA-2 production in reduced ceftazidime and ertapenem susceptibility in a K. pneumon ...[more]

PMID: 31127290

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Project description:UNLABELLED:Carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, pose an urgent threat in health facilities in the United States and worldwide. K. pneumoniae isolates classified as sequence type 258 (ST258) by multilocus sequence typing are largely responsible for the global spread of KPC. A recent comparative genome study revealed that ST258 K. pneumoniae strains are two distinct genetic clades; however, the molecular origin of ST258 largely remains unknown, and our understanding of the evolution of the two genetic clades is incomplete. Here we compared the genetic structures and single-nucleotide polymorphism (SNP) distributions in the core genomes of strains from two ST258 clades and other STs (ST11, ST442, and ST42). We identified an ~1.1-Mbp region on ST258 genomes that is homogeneous to that of ST442, while the rest of the ST258 genome resembles that of ST11. Our results suggest ST258 is a hybrid clone--80% of the genome originated from ST11-like strains and 20% from ST442-like strains. Meanwhile, we sequenced an ST42 strain that carries the same K-antigen-encoding capsule polysaccharide biosynthesis gene (cps) region as ST258 clade I strains. Comparison of the cps-harboring regions between the ST42 and ST258 strains (clades I and II) suggests the ST258 clade I strains evolved from a clade II strain as a result of cps region replacement. Our findings unravel the molecular evolution history of ST258 strains, an important first step toward the development of diagnostic, therapeutic, and vaccine strategies to combat infections caused by multidrug-resistant K. pneumoniae. IMPORTANCE:Recombination events and replacement of chromosomal regions have been documented in various bacteria, and these events have given rise to successful pathogenic clones. Here we used comparative genomic analyses to discover that the ST258 K. pneumoniae genome is a hybrid--80% of the chromosome is homologous to ST11 strains, while the remaining 20% is homologous to that of ST442. Meanwhile, a recent study indicated that ST258 strains can be segregated into two ST258 clades, with distinct capsule polysaccharide gene (cps) regions. Our analysis suggests ST258 clade I strains evolved from clade II through homologous recombination of cps region. Horizontal transfer of the cps region appears to be a key element driving the molecular diversification in K. pneumoniae strains. These findings not only extend our understanding of the molecular evolution of ST258 but are an important step toward the development of effective control and treatment strategies for multidrug-resistant K. pneumoniae.

Dataset Information

Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniae ST258.

Publications

Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniae ST258.

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