Genomic diversity of mcr-carrying plasmids and the role of type IV secretion systems in IncI2 plasmids conjugation
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Updated: May 24, 2025

High-Resolution Comparison of Bacterial Conjugation Frequencies
Published on: January 10, 2019
Zhe Li1, Zhenpeng Li1, Yao Peng1
1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Abstract:
The rapid dissemination of colistin resistance via mcr-carrying plasmids (pMCRs) poses a significant public health challenge. This study examined the genomic diversity and conjugation mechanisms of pMCRs, with a particular focus on the role of type IV secretion systems (T4SS) in IncI2 plasmids. The 868 complete plasmid sequences revealed various replicon types of pMCRs, with IncI2 as the primary epidemic type, and the co-transfer risk of multidrug resistance genes associated with IncHI2. T4SS was identified in 89.9% of pMCRs, with the T4SS sequence exclusively carried by IncI2 being conserved and typical of the VirB/D4 type, consisting of 12 subunits. Conjugation assays confirmed the essential role of the pilus subunit VirB2 and the significant impact of VirB5P3 on conjugation. This was further validated in the in vivo intra-species competitive conjugation of Escherichia coli. Structural predictions show that a hypervariable region at the C-terminus of the pentameric VirB5 co-evolves in sequence with VirB6, and the conserved N-terminal may act as a potential drug target to inhibit the plasmid transfer channel. This study will deepen the understanding of the pMCR epidemic patterns and provide additional insights for controlling the spread of resistant plasmids.
Insights
Colistin resistance plasmids spread rapidly, with IncI2 plasmids being the main type. Understanding their transfer mechanisms, particularly the Type IV Secretion System (T4SS), is key to controlling the spread of antimicrobial resistance.
Area of Science:
- Microbiology
- Genomics
- Molecular Biology
Background:
- Colistin resistance plasmids (pMCRs) are a growing public health threat due to rapid dissemination.
- IncI2 plasmids are the primary epidemic type, often co-carrying multidrug resistance genes.
Purpose of the Study:
- To investigate the genomic diversity and conjugation mechanisms of pMCRs.
- To elucidate the role of Type IV Secretion Systems (T4SS) in IncI2 plasmid transfer.
Main Methods:
- Analysis of 868 complete plasmid sequences.
- Identification and characterization of T4SS components in pMCRs.
- Conjugation assays and in vivo competitive assays in Escherichia coli.
Main Results:
- IncI2 plasmids are the predominant epidemic type of pMCRs.
- T4SS, specifically the VirB/D4 type, is present in 89.9% of pMCRs and crucial for conjugation.
- VirB2 and VirB5 subunits play essential roles in plasmid transfer, with potential drug targets identified in VirB5.
Conclusions:
- The VirB/D4 T4SS is a conserved and essential system for IncI2 plasmid dissemination.
- Understanding the structural and co-evolutionary dynamics of T4SS components can inform strategies to curb the spread of colistin resistance.
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