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Updated: Nov 15, 2025

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Mobile Plasmid Mediated Transition From Colistin-Sensitive to Resistant Phenotype in Klebsiella pneumoniae
Baoyue Zhang1,2, Bing Yu3, Wei Zhou1,2
1CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Abstract:
Multidrug-resistant bacteria, including carbapenem-resistant Klebsiella pneumoniae (CRKP), are becoming an increasing health crisis worldwide. For CRKP, colistin is regarded as "the last treatment option." In this study, we isolated a clinical CRKP strain named as K. pneumoniae R10-341. Phenotyping analysis showed that this strain could transit from a colistin-sensitive to a resistant phenotype by inserting an IS4 family ISKpn72 element into the colistin-resistance associated mgrB gene. To investigate the mechanism of this transition, we performed genome sequencing analysis of the colistin-sensitive parental strain and found that 12 copies of ISKpn72 containing direct repeats (DR) are located on the chromosome and 1 copy without DR is located on a multidrug-resistant plasmid pR10-341_2. Both types of ISKpn72 could be inserted into the mgrB gene to cause colistin-resistance, though the plasmid-derived ISKpn72 without DR was in higher efficiency. Importantly, we demonstrated that colistin-sensitive K. pneumoniae strain transferred with the ISKpn72 element also obtained the ability to switch from colistin-sensitive to colistin-resistant phenotype. Furthermore, we confirmed that the ISKpn72-containing pR10-341_2 plasmid was able to conjugate, suggesting that the ability of causing colistin-resistant transition is transferable through common conjugation. Our results point to new challenges for both colistin-resistance detection and CRKP treatment.
Insights
A mobile genetic element, ISKpn72, enables carbapenem-resistant Klebsiella pneumoniae to switch from colistin-sensitive to resistant. This transition is transferable via conjugation, posing new challenges for treatment and detection.
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- Multidrug-resistant bacteria, particularly carbapenem-resistant Klebsiella pneumoniae (CRKP), represent a global health crisis.
- Colistin is a critical last-resort antibiotic for treating CRKP infections.
- Understanding resistance mechanisms is vital for effective treatment strategies.
Purpose of the Study:
- To investigate the mechanism by which a clinical CRKP strain transitions from colistin sensitivity to resistance.
- To identify the genetic elements involved in this phenotypic switch.
- To assess the transferability of colistin resistance acquisition.
Main Methods:
- Isolation and phenotyping of a clinical CRKP strain (K. pneumoniae R10-341).
- Whole-genome sequencing of the colistin-sensitive parental strain.
- Analysis of ISKpn72 element insertion into the mgrB gene.
- Conjugation experiments to assess transferability of resistance.
Main Results:
- A clinical CRKP strain acquired colistin resistance through the insertion of an ISKpn72 element into the mgrB gene.
- Both chromosomal and plasmid-borne ISKpn72 elements could induce resistance, with the plasmid-derived element showing higher efficiency.
- Transfer of the ISKpn72 element conferred the colistin-resistant transition ability to a sensitive strain.
- The ISKpn72-carrying plasmid was conjugative, indicating transferable resistance acquisition.
Conclusions:
- The ISKpn72 element plays a crucial role in the dynamic transition of K. pneumoniae from colistin sensitivity to resistance.
- The conjugative nature of the ISKpn72-carrying plasmid facilitates the spread of this resistance mechanism.
- These findings highlight significant challenges for colistin resistance detection and CRKP treatment strategies.
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