Disruption of mgrB gene by ISkpn14 sourced from a bla KPC−2 carrying plasmid mediating polymyxin resistance against carbapenem-resistant Klebsiella pneumoniae during treatment: study on the underlying mechanisms

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Title: Disruption of mgrB gene by ISkpn14 sourced from a bla KPC−2 carrying plasmid mediating polymyxin resistance against carbapenem-resistant Klebsiella pneumoniae during treatment: study on the underlying mechanisms
Authors: Ziyao Li, Zichen Lei, Xinmeng Liu, Feilong Zhang, Xinrui Yang, Yongli Wu, Chen Li, Jiankang Zhao, Yulin Zhang, Yanning Hua, Binghuai Lu, Bin Cao
Source: BMC Microbiology, Vol 24, Iss 1, Pp 1-12 (2024)
Publisher Information: BMC, 2024.
Publication Year: 2024
Collection: LCC:Microbiology
Subject Terms: Polymyxin resistance, Insertion sequence, Carbapenem-resistant Klebsiella pneumoniae, Acquired resistance, Origination of the IS, Microbiology, QR1-502
More Details: Abstract Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections poses global challenges, with limited options available for targeted therapy. Polymyxin was been regarded as one of the most important last-resort antimicrobial agents. Many factors could accelerate the resistance evolution of polymyxin. Insertion sequence (IS) inserted into mgrB is the main polymyxin resistance mechanism in K. pneumoniae. In this study, two CRKPs (KP31157 and KP31311) were isolated from the urine of a patient, shifting from susceptible to resistant as the mgrB inserted by ISkpn14. We intended to explore the origin of the IS and underlying mechanisms resulting in polymyxin resistance. Methods The within-host evolution relationship and molecular features of both CRKPs were determined by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). pKP31311_KPC-2 plasmid genome structures contained in the above two CRKPs were aligned with the homologic plasmids, retrieved from the NCBI genome database via comparative genomic analysis. The plasmids encoding ISkpn14 elements flanked by direct repeat (DR) or not were analyzed. The mRNA expression, plasmid curing and in vitro antibiotics inducing experiment were employed to understand the potential mechanism of polymyxin resistance. Results Both strains, sharing homology, exhibited polymyxin resistance due to the insertion of ISkpn14 into the mgrB gene, influenced by minocycline exposure. Minocycline and tigecycline could accelerate polymyxin resistance (P
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1471-2180
Relation: https://doaj.org/toc/1471-2180
DOI: 10.1186/s12866-024-03572-2
Access URL: https://doaj.org/article/0c01922e3d354ef0bc3e7f59bec75163
Accession Number: edsdoj.0c01922e3d354ef0bc3e7f59bec75163
Database: Directory of Open Access Journals
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ISSN:14712180
DOI:10.1186/s12866-024-03572-2
Published in:BMC Microbiology
Language:English