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Resolving structural diversity of Carbapenemase-producing gram-negative bacteria using single molecule sequencing

View ORCID ProfileNicholas Noll, Eric Urich, Daniel Wüthrich, Vladimira Hinic, Adrian Egli, View ORCID ProfileRichard A. Neher
doi: https://doi.org/10.1101/456897
Nicholas Noll
1Biozentrum, University of Basel, Basel, Switzerland
2Swiss Institute of Bioinformatics, Basel, Switzerland
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  • ORCID record for Nicholas Noll
Eric Urich
1Biozentrum, University of Basel, Basel, Switzerland
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Daniel Wüthrich
3Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland
4Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland
2Swiss Institute of Bioinformatics, Basel, Switzerland
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Vladimira Hinic
3Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland
4Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland
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Adrian Egli
3Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland
4Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland
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Richard A. Neher
1Biozentrum, University of Basel, Basel, Switzerland
2Swiss Institute of Bioinformatics, Basel, Switzerland
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  • ORCID record for Richard A. Neher
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Abstract

Carbapenemase-producing bacteria are resistant against almost all commonly used betalactam and cephalosporin antibiotics and represent a growing public health crisis. Carbapenemases reside predominantly in mobile genetic elements and rapidly spread across genetic backgrounds and species boundaries. Here, we report more than one hundred finished, high quality genomes of carbapenemase producing enterobacteriaceae, P. aeruginosa and A. baumannii sequenced with Oxford Nanopore and Illumina technologies. We developed a number of high-throughput criteria to assess the quality of fully assembled genomes for which curated references do not exist. Using this diverse collection of closed genomes and plasmids, we demonstrate rapid movement of carbapenemase between genomic neighborhoods, sequence types, and across species boundaries with distinct patterns for different carbapenemases. Lastly, we present evidence of multiple ancestral recombination events between different Enterobacteriaceae MLSTs. Taken together, our samples suggest a hierarchical picture of genomic variation produced by the evolution of carbapenemase producing bacteria that will require new models to adequately understand and track.

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Posted October 30, 2018.
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Resolving structural diversity of Carbapenemase-producing gram-negative bacteria using single molecule sequencing
Nicholas Noll, Eric Urich, Daniel Wüthrich, Vladimira Hinic, Adrian Egli, Richard A. Neher
bioRxiv 456897; doi: https://doi.org/10.1101/456897
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Resolving structural diversity of Carbapenemase-producing gram-negative bacteria using single molecule sequencing
Nicholas Noll, Eric Urich, Daniel Wüthrich, Vladimira Hinic, Adrian Egli, Richard A. Neher
bioRxiv 456897; doi: https://doi.org/10.1101/456897

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