Related Experiment Video

Updated: Jun 26, 2026

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
09:00

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

Published on: May 2, 2018

11.7K

Complex evolutionary trajectories in vivo of two novel KPC variants conferring ceftazidime-avibactam resistance

Chengkang Tang1, Siquan Shen1, Weiwei Yang1

  • 1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.

International Journal of Antimicrobial Agents
|July 4, 2024
PubMed

Insights

Novel KPC variants in Klebsiella pneumoniae confer ceftazidime-avibactam resistance and impact carbapenem susceptibility. Understanding these evolutionary changes is crucial for effective antimicrobial stewardship and patient treatment strategies.

Area of Science:

  • Molecular biology and microbiology
  • Antimicrobial resistance mechanisms
  • Bacterial evolution and adaptation

Background:

  • Increasing prevalence of ceftazidime-avibactam-resistant Klebsiella pneumoniae strains producing KPC variants.
  • Limited understanding of the evolutionary pathways and fitness consequences associated with KPC mutations.

Purpose of the Study:

  • To investigate the in vivo evolution of novel KPC variants (KPC-155 and KPC-185) in Klebsiella pneumoniae.
  • To determine the resistance profiles and fitness effects of these KPC variants.
  • To elucidate the role of genetic elements like IS26 in the amplification and spread of KPC genes.

Main Methods:

  • Plasmid transformation assays, cloning experiments, and enzyme kinetic measurements to assess resistance.
  • In vitro competition experiments and growth curve analyses to evaluate strain fitness.
  • Comparative plasmid analysis and investigation of IS26-mediated transposition events.

Main Results:

  • Two novel KPC variants, KPC-155 and KPC-185, were identified, conferring ceftazidime-avibactam resistance while restoring carbapenem susceptibility.
  • Strains with these variants exhibited an adaptive advantage in vitro, promoting rapid spread.
  • IS26-mediated replicative transposition led to blaKPC amplification, but double copies reduced competitive advantage and stability.

Conclusions:

  • The evolution of KPC variants involves complex in vivo trajectories and confers significant selective advantages.
  • IS26-containing elements play a role in the dissemination and amplification of KPC resistance genes.
  • Continuous monitoring of antimicrobial susceptibility and KPC subtypes is essential during treatment, particularly with ceftazidime-avibactam.
Keywords:
Ceftazidime-avibactamFitnessIS26KPC variantsKlebsiella pneumoniae

More Related Videos

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes08:23

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes

Published on: March 2, 2020

12.7K
Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System05:06

Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System

Published on: January 5, 2024

580

Related Concept Videos

Antibiotic Selection00:57

Antibiotic Selection

Overview
Genome Size and the Evolution of New Genes03:21

Genome Size and the Evolution of New Genes

While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
Evolution of New Traits in Microbes01:24

Evolution of New Traits in Microbes

Microorganisms evolve rapidly due to their large population sizes and short generation times, often exhibiting measurable changes within days under laboratory conditions. Natural selection acts on standing genetic variation, enabling the retention and amplification of beneficial traits that confer fitness advantages in changing environments.Adaptive Pigment Regulation in RhodobacterIn Rhodobacter, a genus of purple non-sulfur bacteria, light-harvesting pigments such as bacteriochlorophyll and...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...