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Updated: Jun 27, 2026
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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Novel continuous experimental evolution methodology uncovers rapid resistance development and cross-resistance
Thaddäus Echelmeyer1, Markus Ellmann1, Stefan E Heiden1
1Department of Epidemiology and Ecology of Antimicrobial Resistance, Helmholtz Institute for One Health, Helmholtz Centre for Infection Research, Greifswald, Germany.
Npj Antimicrobials and Resistance
|March 3, 2026
Summary
A new experimental evolution system rapidly identified cefepime-resistant Enterobacter cloacae. A single mutation in blaMIR-11 caused cross-resistance to novel antibiotics, highlighting risks of antimicrobial resistance development.
Area of Science:
- Microbiology
- Molecular Biology
- Evolutionary Biology
Background:
- Antimicrobial resistance (AMR) is a critical global health challenge.
- Experimental evolution aids understanding of resistance mechanisms and antibiotic preservation strategies.
- Enterobacter cloacae complex strains are significant human pathogens.
Purpose of the Study:
- To develop and validate a novel continuous experimental evolution system for studying AMR.
- To investigate cefepime resistance development in Enterobacter cloacae.
- To identify resistance mechanisms and potential cross-resistance to novel antibiotics.
Main Methods:
- Development of a continuous experimental evolution system with a rising antibiotic gradient.
- Application of the system to three cefepime-naive Enterobacter cloacae complex strains.
- Genomic analysis to identify mutations conferring resistance.
Main Results:
- Resistant mutants emerged within four days of cefepime exposure in all strains.
- One mutant displayed cross-resistance to cefiderocol and ceftazidime-avibactam.
- A single missense mutation in blaMIR-11 was identified as the cause of major cross-resistance.
Conclusions:
- The novel experimental evolution system is effective for studying AMR development.
- A blaMIR-11 mutation confers significant cross-resistance, posing a threat to current and future antibiotic efficacy.
- Understanding resistance mechanisms is crucial for preserving antibiotic effectiveness.
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