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.

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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