Dataset Information

Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacter xylosoxidans.

ABSTRACT: The development of antibiotic resistance during treatment is a threat to patients and their environment. Insight in the mechanisms of resistance development is important for appropriate therapy and infection control. Here, we describe how through the application of mass spectrometry-based proteomics, a novel beta-lactamase Axc was identified as an indicator of acquired carbapenem resistance in a clinical isolate of Achromobacter xylosoxidans. Comparative proteomic analysis of consecutively collected susceptible and resistant isolates from the same patient revealed that high Axc protein levels were only observed in the resistant isolate. Heterologous expression of Axc in Escherichia coli significantly increased the resistance towards carbapenems. Importantly, direct Axc mediated hydrolysis of imipenem was demonstrated using pH shift assays and 1H-NMR, confirming Axc as a legitimate carbapenemase. Whole genome sequencing revealed that the susceptible and resistant isolates were remarkably similar. Together these findings provide a molecular context for the fast development of meropenem resistance in A. xylosoxidans during treatment and demonstrate the use of mass spectrometric techniques in identifying novel resistance determinants.

SUBMITTER: Fleurbaaij F

PROVIDER: S-EPMC5970244 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacter xylosoxidans.

Fleurbaaij Frank F Henneman Alex A AA Corver Jeroen J Knetsch Cornelis W CW Knetsch Cornelis W CW Smits Wiep Klaas WK Nauta Sjoerd T ST Giera Martin M Dragan Irina I Kumar Nitin N Lawley Trevor D TD Verhoeven Aswin A van Leeuwen Hans C HC Kuijper Ed J EJ Hensbergen Paul J PJ

Scientific reports 20180525 1

The development of antibiotic resistance during treatment is a threat to patients and their environment. Insight in the mechanisms of resistance development is important for appropriate therapy and infection control. Here, we describe how through the application of mass spectrometry-based proteomics, a novel beta-lactamase Axc was identified as an indicator of acquired carbapenem resistance in a clinical isolate of Achromobacter xylosoxidans. Comparative proteomic analysis of consecutively colle ...[more]

PMID: 29802257

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Project description:Chromosomal co-existence of metal and antibiotic resistance genes in bacteria offers a new perspective to the bacterial resistance proliferation in contaminated environment. In this study, an arsenotrophic bacterium Achromobacter xylosoxidans BHW-15, isolated from Arsenic (As) contaminated tubewell water in the Bogra district of Bangladesh, was analyzed using high throughput Ion Torrent Personal Genome Machine (PGM) complete genome sequencing scheme to reveal its adaptive potentiality. The assembled draft genome of A. xylosoxidans BHW-15 was 6.3 Mbp containing 5,782 functional genes, 1,845 pseudo genes, and three incomplete phage signature regions. Comparative genome study suggested the bacterium to be a novel strain of A. xylosoxidans showing significant dissimilarity with other relevant strains in metal resistance gene islands. A total of 35 metal resistance genes along with arsenite-oxidizing aioSXBA, arsenate reducing arsRCDAB, and mercury resistance merRTPADE operonic gene cluster and 20 broad range antibiotic resistance genes including β-lactams, aminoglycosides, and multiple multidrug resistance (MDR) efflux gene complex with a tripartite system OM-IM-MFP were found co-existed within the genome. Genomic synteny analysis with reported arsenotrophic bacteria revealed the characteristic genetic organization of ars and mer operonic genes, rarely described in β-Proteobacteria. A transposon Tn21 and mobile element protein genes were also detected to the end of mer (mercury) operonic genes, possibly a carrier for the gene transposition. In vitro antibiotic susceptibility assay showed a broad range of resistance against antibiotics belonging to β-lactams, aminoglycosides, cephalosporins (1st, 2nd, and 3rd generations), monobactams and even macrolides, some of the resistome determinants were predicted during in silico analysis. KEGG functional orthology analysis revealed the potential of the bacterium to utilize multiple carbon sources including one carbon pool by folate, innate defense mechanism against multiple stress conditions, motility, a proper developed cell signaling and processing unit and secondary metabolism-combination of all exhibiting a robust feature of the cell in multiple stressed conditions. The complete genome of the strain BHW-15 stands as a genetic basis for the evolutionary adaptation of metal and the antibiotic coexistence phenomenon in an aquatic environment.

Dataset Information

Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacter xylosoxidans.

Publications

Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacter xylosoxidans.

Similar Datasets

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