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Published on: March 1, 2022
Assessing genetic diversity and similarity of 435 KPC-carrying plasmids
Christian Brandt1,2, Adrian Viehweger3,4, Abhijeet Singh5
1Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany. christian.jena@gmail.com.
Abstract:
The global spread and diversification of multidrug-resistant Gram-negative (MRGN) bacteria poses major challenges to healthcare. In particular, carbapenem-resistant Klebsiella pneumoniae strains have been frequently identified in infections and hospital-wide outbreaks. The most frequently underlying resistance gene (blaKPC) has been spreading over the last decade in the health care setting. blaKPC seems to have rapidly diversified and has been found in various species and on different plasmid types. To review the progress and dynamics of this diversification, all currently available KPC plasmids in the NCBI database were analysed in this work. Plasmids were grouped into 257 different representative KPC plasmids, of which 79.4% could be clearly assigned to incompatibility (Inc) group or groups. In almost half of all representative plasmids, the KPC gene is located on Tn4401 variants, emphasizing the importance of this transposon type for the transmission of KPC genes to other plasmids. The transposons also seem to be responsible for the occurrence of altered or uncommon fused plasmid types probably due to incomplete transposition. Moreover, many KPC plasmids contain genes that encode proteins promoting recombinant processes and mutagenesis; in consequence accelerating the diversification of KPC genes and other colocalized resistance genes.
Insights
Multidrug-resistant Gram-negative bacteria, especially carbapenem-resistant Klebsiella pneumoniae, are a growing threat. Analysis of KPC plasmids reveals rapid diversification driven by transposons like Tn4401, accelerating antimicrobial resistance spread.
Area of Science:
- Microbiology
- Genetics
- Public Health
Background:
- Multidrug-resistant Gram-negative (MRGN) bacteria, particularly carbapenem-resistant Klebsiella pneumoniae, present significant healthcare challenges.
- The blaKPC gene, a primary driver of carbapenem resistance, has spread globally in healthcare settings over the past decade.
Purpose of the Study:
- To investigate the diversification and spread dynamics of carbapenemase-producing Klebsiella pneumoniae (KPC) plasmids.
- To analyze the genetic elements and mechanisms contributing to KPC gene dissemination.
Main Methods:
- Bioinformatic analysis of all available KPC plasmids in the NCBI database.
- Classification of plasmids into incompatibility (Inc) groups and identification of associated genetic elements, including transposons.
Main Results:
- 257 representative KPC plasmids were identified, with 79.4% assigned to specific Inc groups.
- The Tn4401 transposon and its variants were found in nearly half of the analyzed plasmids, facilitating KPC gene transfer.
- Plasmids frequently contained genes promoting recombination and mutagenesis, accelerating resistance gene diversification.
Conclusions:
- The diversification of KPC plasmids is significantly influenced by the Tn4401 transposon and plasmid-borne accessory genes.
- These genetic mechanisms contribute to the rapid spread and evolution of carbapenem resistance in Klebsiella pneumoniae, posing an ongoing public health concern.
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