Disruption of mgrB gene by ISkpn14 sourced from a bla
Klebsiella pneumoniae
/ genetics
Plasmids
/ genetics
Humans
Polymyxins
/ pharmacology
Anti-Bacterial Agents
/ pharmacology
Klebsiella Infections
/ microbiology
beta-Lactamases
/ genetics
Carbapenems
/ pharmacology
Microbial Sensitivity Tests
Bacterial Proteins
/ genetics
Carbapenem-Resistant Enterobacteriaceae
/ genetics
Whole Genome Sequencing
DNA Transposable Elements
/ genetics
Drug Resistance, Bacterial
/ genetics
Acquired resistance
Carbapenem-resistant Klebsiella pneumoniae
Insertion sequence
Origination of the IS
Polymyxin resistance
Journal
BMC microbiology
ISSN: 1471-2180
Titre abrégé: BMC Microbiol
Pays: England
ID NLM: 100966981
Informations de publication
Date de publication:
22 Oct 2024
22 Oct 2024
Historique:
received:
10
03
2024
accepted:
08
10
2024
medline:
23
10
2024
pubmed:
23
10
2024
entrez:
22
10
2024
Statut:
epublish
Résumé
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. 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. 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 This study provides direct experimental evidence that the ISkpn14 element causing mgrB inactivation and polymyxin resistance in K. pneumoniae originates from bla
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
CONCLUSIONS
This study provides direct experimental evidence that the ISkpn14 element causing mgrB inactivation and polymyxin resistance in K. pneumoniae originates from bla
Identifiants
pubmed: 39438834
doi: 10.1186/s12866-024-03572-2
pii: 10.1186/s12866-024-03572-2
doi:
Substances chimiques
Polymyxins
0
Anti-Bacterial Agents
0
beta-Lactamases
EC 3.5.2.6
Carbapenems
0
Bacterial Proteins
0
DNA Transposable Elements
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
422Subventions
Organisme : Beijing Natural Science Foundation
ID : 7242124
Organisme : The CAMS Innovation Fund for Medical Sciences
ID : CIFMS; No.2021-I2M-1-030
Informations de copyright
© 2024. The Author(s).
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