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Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach
Published on: December 14, 2019
Convergence of plasmid-driven virulence and antibiotic resistance in Escherichia coli
Zheng Jie Lian1,2, Nguyen Thi Khanh Nhu1,2, Chitra Ravi1,2,3
1Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Abstract:
Plasmids are major vehicles for the spread of antibiotic resistance genes. Some plasmids additionally carry virulence genes that enhance host pathogenicity. The convergence of resistance and virulence genes on the same plasmid poses significant risk, providing a mechanism to create pathogens that cause severe disease with limited treatment options. Colicin V (ColV)-like plasmids (ColVLPs) are virulence plasmids frequently carried by extra-intestinal pathogenic E. coli (ExPEC) that cause human and avian infection. Here, by generating and analysing a ColVLP database, we demonstrate that ColVLPs form four distinct sub-groups, characterised by genes encoding for Colicins V and M, with differing virulence and antimicrobial resistance gene carriage. Three of these sub-groups possess moderate-high resistance towards multiple antibiotic classes. We further describe ColVLP co-integrates that have acquired extensive resistance profiles, including against last line colistin, through recombination with co-resident plasmids. Using pMS7163A, a ColVLP from a virulent ExPEC strain, we also demonstrate that the ColVLP-encoded outer membrane protease virulence factor OmpTp works co-operatively with its chromosomal homolog to enhance ExPEC resistance against human cathelicidin (LL-37), an antimicrobial peptide expressed in the urinary tract. Together, our work characterises ColVLPs as high-risk mobile genetic elements that amplify the convergence of resistance and virulence in ExPEC.
Insights
Colicin V-like plasmids (ColVLPs) in E. coli amplify antibiotic resistance and virulence. These high-risk elements create dangerous pathogens with limited treatment options.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Plasmids facilitate the spread of antibiotic resistance genes (ARGs) and virulence genes (VGs).
- The co-location of ARGs and VGs on plasmids creates pathogens with enhanced pathogenicity and resistance.
- Colicin V-like plasmids (ColVLPs) are key virulence plasmids in extra-intestinal pathogenic E. coli (ExPEC).
Purpose of the Study:
- To characterize ColVLPs and their association with antibiotic resistance and virulence.
- To investigate the role of ColVLPs in the convergence of resistance and virulence in ExPEC.
- To analyze the contribution of specific ColVLP-encoded factors to ExPEC pathogenicity.
Main Methods:
- Generation and analysis of a ColVLP database.
- Sub-grouping of ColVLPs based on gene content.
- Characterization of ColVLP co-integrates and their resistance profiles.
- Experimental validation of the role of OmpTp in ExPEC resistance to antimicrobial peptides.
Main Results:
- ColVLPs form four distinct sub-groups with varying virulence and antimicrobial resistance gene carriage.
- Three ColVLP sub-groups exhibit moderate-to-high resistance to multiple antibiotic classes.
- ColVLP co-integrates show extensive resistance, including to colistin.
- The OmpTp protease enhances ExPEC resistance to the human cathelicidin LL-37.
Conclusions:
- ColVLPs are high-risk mobile genetic elements that drive the convergence of resistance and virulence in ExPEC.
- These plasmids contribute to the emergence of severe, difficult-to-treat ExPEC infections.
- Understanding ColVLP biology is crucial for combating antimicrobial resistance and pathogenicity in E. coli.
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