Multiple-Replicon Resistance Plasmids of Klebsiella Mediate Extensive Dissemination of Antimicrobial Genes

Abstract

Multiple-replicon resistance plasmids have become important carriers of resistance genes in Gram-negative bacteria, and the evolution of multiple-replicon plasmids is still not clear. Here, 56 isolates of Klebsiella isolated from different wild animals and environments between 2018 and 2020 were identified by phenotyping via the micro-broth dilution method and were sequenced and analyzed for bacterial genome-wide association study. Our results revealed that the isolates from non-human sources showed more extensive drug resistance and especially strong resistance to ampicillin (up to 80.36%). The isolates from Malayan pangolin were particularly highly resistant to cephalosporins, chloramphenicol, levofloxacin, and sulfamethoxazole. Genomic analysis showed that the resistance plasmids in these isolates carried many antibiotic resistance genes. Further analysis of 69 plasmids demonstrated that 28 plasmids were multiple-replicon plasmids, mainly carrying beta-lactamase genes such as blaCTX–M–15, blaCTX–M–14, blaCTX–M–55, blaOXA–1, and blaTEM–1. The analysis of plasmids carried by different isolates showed that Klebsiella pneumoniae might be an important multiple-replicon plasmid host. Plasmid skeleton and structure analyses showed that a multiple-replicon plasmid was formed by the fusion of two or more single plasmids, conferring strong adaptability to the antibiotic environment and continuously increasing the ability of drug-resistant isolates to spread around the world. In conclusion, multiple-replicon plasmids are better able to carry resistance genes than non-multiple-replicon plasmids, which may be an important mechanism underlying bacterial responses to environments with high-antibiotic pressure. This phenomenon will be highly significant for exploring bacterial resistance gene transmission and diffusion mechanisms in the future.

Phylogenomics of globally spread Clonal Groups 14 and 15 of Klebsiella pneumoniae

“…Carriage of genes encoding adaptive functions (antimicrobial resistance, metal tolerance, thermoresistance, amongst others) reflects a history of exposure to disparate selection pressures (54). The high degree of mosaicism observed, especially on F-type plasmids is in agreement with previous observations, and is suggestive of the impact of recombination in the dissemination of ARGs (56, 57). The high level of recombination between highly similar plasmids and replicons, and the narrow host range of most plasmid groups (at the genus- Klebsiella and family- Enterobacteriaceae level) suggests a degree of specialization that results from the long-term co-evolution of these plasmid types in this genetic background ( Figure S6 ) (55).…”

Antimicrobial Resistance and Mechanisms of Azithromycin Resistance in Nontyphoidal Salmonella Isolates in Taiwan, 2017 to 2018

“…As shown in Table 7 , IncHI2-IncHI2A plasmids are usually very large (181 kb to 299 kb) and can carry a large number of resistance genes. IncHI2-IncHI2A plasmids may be able to stably merge with other replicons so that they can acquire more resistance genes ( 42 ). We previously reported an mph (A)-carrying IncHI2-IncHI2A plasmid that was capable of moving from an S. Typhimurium strain to an Escherichia coli strain through conjugation ( 22 ).…”

Genetic Diversity and Pathogenic Features in Klebsiella pneumoniae Isolates from Patients with Pyogenic Liver Abscess and Pneumonia

“…Pneumonia patient-sourced isolates carried more replicons than those from other sources. Previous studies have demonstrated that multiple-replicon plasmids are more capable of carrying resistance genes than non-multiple-replicon plasmids, which may be a vital mechanism underlying Klebsiella responses to high antibiotic pressure ( 27 , 28 ). Much of the antimicrobial resistance of K. pneumoniae is a consequence of acquired plasmids, and plasmids such as IncFIIK have been associated with the expression of carbapenemase ( 29 ).…”