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

Ziyao Li; Zichen Lei; Xinmeng Liu; Feilong Zhang; Xinrui Yang; Yongli Wu; Chen Li; Jiankang Zhao; Yulin Zhang; Yanning Hua; Binghuai Lu; Bin Cao

doi:10.1186/s12866-024-03572-2

BMC Microbiology (Oct 2024)

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

Ziyao Li,
Zichen Lei,
Xinmeng Liu,
Feilong Zhang,
Xinrui Yang,
Yongli Wu,
Chen Li,
Jiankang Zhao,
Yulin Zhang,
Yanning Hua,
Binghuai Lu,
Bin Cao

Affiliations

Ziyao Li: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Zichen Lei: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Xinmeng Liu: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Feilong Zhang: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Xinrui Yang: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Yongli Wu: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Chen Li: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Jiankang Zhao: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Yulin Zhang: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Yanning Hua: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Binghuai Lu: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital
Bin Cao: Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital

DOI: https://doi.org/10.1186/s12866-024-03572-2
Journal volume & issue: Vol. 24, no. 1
pp. 1 – 12

Abstract

Read online

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 < 0.05), validated by an in vitro induction experiment. The ISkpn14 without DR flanked expressed about 4 times higher than that with DR. The frequency of the mgrB insertion induced by polymyxin was significantly reduced (0 strain detected) after the bla KPC−2-carrying plasmid was eliminated. Conclusions This study provides direct experimental evidence that the ISkpn14 element causing mgrB inactivation and polymyxin resistance in K. pneumoniae originates from bla KPC−2-carrying plasmids. Minocycline exposure will accelerate the evolution of polymyxin resistance. Understanding the dynamics of IS transposition and its association with antibiotic exposure is crucial for developing effective strategies to reduce the emergence of polymyxin resistance in CRKP.

Published in BMC Microbiology

ISSN: 1471-2180 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Science: Microbiology
Website: http://www.biomedcentral.com/bmcmicrobiol/

About the journal

Abstract

Keywords