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Updated: Dec 26, 2025

Replication of the Ordered, Nonredundant Library of Pseudomonas aeruginosa strain PA14 Transposon Insertion Mutants
Published on: May 4, 2018
A megaplasmid family driving dissemination of multidrug resistance in Pseudomonas
Adrian Cazares1, Matthew P Moore2, James P J Hall3
1Institute of Infection and Global Health, University of Liverpool, Liverpool, UK. A.Cazares-Lopez@liverpool.ac.uk.
Abstract:
Multidrug resistance (MDR) represents a global threat to health. Here, we used whole genome sequencing to characterise Pseudomonas aeruginosa MDR clinical isolates from a hospital in Thailand. Using long-read sequence data we obtained complete sequences of two closely related megaplasmids (>420 kb) carrying large arrays of antibiotic resistance genes located in discrete, complex and dynamic resistance regions, and revealing evidence of extensive duplication and recombination events. A comprehensive pangenomic and phylogenomic analysis indicates that: 1) these large plasmids comprise an emerging family present in different members of the Pseudomonas genus, and associated with multiple sources (geographical, clinical or environmental); 2) the megaplasmids encode diverse niche-adaptive accessory traits, including multidrug resistance; 3) the accessory genome of the megaplasmid family is highly flexible and diverse. The history of the megaplasmid family, inferred from our analysis of the available database, suggests that members carrying multiple resistance genes date back to at least the 1970s.
Insights
Multidrug resistance (MDR) in Pseudomonas aeruginosa is a major health concern. This study characterized large plasmids carrying antibiotic resistance genes, revealing their ancient origins and flexible nature.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Multidrug resistance (MDR) in bacteria poses a significant global health threat.
- Pseudomonas aeruginosa is a common opportunistic pathogen frequently associated with hospital-acquired infections and MDR.
Purpose of the Study:
- To characterize the whole genome of multidrug-resistant Pseudomonas aeruginosa clinical isolates.
- To investigate the structure, evolution, and diversity of large plasmids carrying antibiotic resistance genes.
Main Methods:
- Whole genome sequencing using long-read technology.
- Pangenomic and phylogenomic analyses.
- Comparative analysis of plasmid sequences.
Main Results:
- Complete sequences of two large (>420 kb) megaplasmids from P. aeruginosa isolates were obtained.
- These megaplasmids harbor extensive arrays of antibiotic resistance genes within complex and dynamic regions.
- Phylogenomic analysis revealed an emerging family of these megaplasmids across the Pseudomonas genus, dating back to at least the 1970s.
- The megaplasmids encode diverse accessory traits and exhibit a highly flexible and diverse accessory genome.
Conclusions:
- Large, complex megaplasmids are key drivers of multidrug resistance in Pseudomonas aeruginosa.
- This megaplasmid family is ancient, widespread, and evolves through duplication and recombination.
- Understanding these mobile genetic elements is crucial for combating antimicrobial resistance.
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