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Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach
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Formation, Transmission, and Dynamic Evolution of a Multidrug-Resistant Chromosomally Integrated Plasmid in

Man-Xia Chang1,2, Jing Zhang1, Jin-Fei Zhang1

  • 1Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

Frontiers in Microbiology
|April 25, 2022
PubMed

Insights

This study reveals how a multidrug-resistant chromosomally integrated plasmid (MRCP) in Salmonella evolves and transmits. It demonstrates MRCP

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • IncHI2 plasmids are highly flexible and contribute to antibiotic resistance acquisition and spread.
  • The formation, excision, and evolution of multidrug-resistant chromosomally integrated plasmids (MRCPs) remain poorly understood.
  • Previous research has not identified polymorphic mobile genetic elements (MGEs) derived from chromosomally integrated IncHI2 plasmids.

Purpose of the Study:

  • To investigate the mechanisms behind the formation, excision, and dynamic evolution of a multidrug-resistant chromosomally integrated plasmid (MRCP).
  • To characterize the genetic elements and processes involved in MRCP generation and transmission.
  • To understand the implications of MRCP's flexible existence for antibiotic resistance.

Main Methods:

  • Identification and characterization of a 260-kb IncHI2 plasmid carrying blaCTX-M-55 and qnrS1 in a Salmonella Muenster strain.
  • Conjugation experiments to transfer the MRCP into E. coli J53, followed by analysis of generated MGEs.
  • Bioinformatic analysis of IS26 elements and truncated Tn1721 involvement.
  • Stability and growth kinetics assays of MRCP progeny.

Main Results:

  • A 260-kb blaCTX-M-55-qnrS1-bearing IncHI2 plasmid was identified and termed MRCP.
  • Conjugation yielded heterogeneous MGEs, including new E. coli chromosomally integrated plasmids and circular plasmids.
  • Replicative transposition and homologous recombination of IS26, along with truncated Tn1721, were key in MRCP offspring formation.
  • Released MRCP could capture adjacent chromosomal segments, forming larger plasmid progeny.
  • MRCP progeny exhibited differentiated biological characteristics, stability, and growth kinetics.

Conclusions:

  • The study provides insights into the flexible existence and evolution of MRCPs.
  • The conversion between vertical and horizontal transmission provides MRCPs with genetic stability and transferability.
  • This adaptability in MRCPs may accelerate antibiotic resistance acquisition and persistence in pathogens, posing challenges to treatment.
Keywords:
Hfr straincointegrateheterogeneous mobile genetic elementshomologous recombinationmultidrug resistance

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