Antibiotics | Novel Mobilization Mechanism of the blaKPC Gene in Pseudomonas aeruginosa

This study reveals novel genetic mobile platforms of blaKPC-2 and blaKPC-3 genes in Pseudomonas aeruginosa, including Tn2-derived non-Tn4401 elements (NTEKPC-IIg) and ISPa38/TnPa38 insertion events. These findings provide critical insights into the dissemination of antibiotic resistance in Pseudomonas aeruginosa.

 

Literature Overview
This article, 'Novel Mobilization Mechanism of blaKPC Gene in Pseudomonas aeruginosa: Acquisition of blaKPC-3 and Identification of a New Tn2-like NTE Mobilizing blaKPC-2,' published in the journal Antibiotics, reviews the genetic platform characteristics of blaKPC genes in epidemic clones ST111 and ST235 of Pseudomonas aeruginosa from Colombia.

Background Knowledge
Carbapenem antibiotics have long been considered the last resort for treating multidrug-resistant bacterial infections, while the emergence and spread of blaKPC genes have significantly reduced their efficacy. Pseudomonas aeruginosa, a conditionally pathogenic bacterium prevalent in hospital environments, exhibits complex and diverse resistance mechanisms, including outer membrane porin protein deficiency, efflux pump overexpression, and acquisition of carbapenemases (e.g., KPC and VIM). Initially identified in Klebsiella species, blaKPC genes have recently disseminated into Pseudomonas aeruginosa, particularly in epidemic clones ST111 and ST235. This study identifies novel mobile elements in these clones, including Tn2-derived NTEKPC-IIg structures and ISPa38/TnPa38-mediated chromosomal integration mechanisms. Characterization of these genetic elements is critical for understanding their stabilization and dissemination across plasmid and chromosomal platforms.

 

 

Research Methods and Experiments
The study collected 128 carbapenem-resistant Pseudomonas aeruginosa isolates from six major hospitals in Colombia, of which 66 carried blaKPC genes. Whole-genome sequencing (WGS) and comparative genomic analysis were employed to characterize the genetic platforms of blaKPC-2 and blaKPC-3, examining their associations with plasmids and transposons. Special focus was placed on mobilization mechanisms of blaKPC genes in ST111 and ST235 clones, including plasmid structures, insertion sequences (IS), and features of non-Tn4401 genetic elements.

Key Conclusions and Perspectives

• blaKPC-3 gene spreads via Tn4401b plasmids in ST111 clones and integrates into chromosomes through ISPa38/TnPa38 insertions in certain strains.
• blaKPC-2 gene in ST235 clones is mediated by a novel Tn2-derived non-Tn4401 genetic element (NTEKPC-IIg), which does not belong to known plasmid incompatibility groups and lacks additional resistance genes.
• Researchers identified ISKmi1 insertions from the IS30 transposon family upstream of blaKPC-2, introducing novel promoter regions that may influence gene expression regulation.
• blaKPC-2 and blaKPC-3 genes show widespread dissemination across Colombian hospitals, with NTEKPC-IIg detected in 18 isolates (27.3%) from five hospitals, highlighting its strong diffusion capacity.
• ISPa38/TnPa38 represents a novel transposon structure forming pseudo-compound transposons in ST111 clones, potentially facilitating stable blaKPC gene integration via replicative transposition mechanisms.

Research Significance and Prospects
This work first identifies plasmid-mediated dissemination of blaKPC-3 in Pseudomonas aeruginosa and novel mobilization mechanisms for blaKPC-2 via Tn2-NTEKPC-IIg structures. These results emphasize the ongoing evolution of carbapenemase genes under diverse mobile genetic elements (MGEs) and the global transmission potential of high-risk clones. Future efforts should prioritize genomic surveillance to track resistance element dissemination and investigate stabilization mechanisms in clinical settings.

 

 

Conclusion
The continuous dissemination of blaKPC genes is a key driver of multidrug-resistant Pseudomonas aeruginosa spread. This study identifies two novel blaKPC mobilization platforms in Colombian clinical isolates: Tn2-derived NTEKPC-IIg and ISPa38/TnPa38-mediated chromosomal integration. These findings indicate that blaKPC gene transmission relies not only on classical Tn4401 transposition but also synergistic interactions with other transposons and insertion sequences. Therefore, genomic surveillance and molecular epidemiology studies are crucial for resistance control. Future work should investigate the molecular mechanisms of these novel mobile elements and their potential impacts on bacterial adaptability and pathogenicity to inform improved infection control strategies.

 

Deisy Abril, Juan Bravo-Ojeda, Julio-Cesar Garcia, Natasha Vanegas Gómez, and Javier Escobar-Pérez. New Insights in blaKPC Gene Mobilization in Pseudomonas aeruginosa: Acquisition of blaKPC-3 and Identification of a New Tn2-like NTE Mobilizing blaKPC-2. Antibiotics.