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Updated: Feb 22, 2026

Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing
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Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing

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Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae

Lisa M Leung1, Vaughn S Cooper2,3, David A Rasko4

  • 1Department of Microbial Pathogenesis, School of Dentistry, University of Maryland Baltimore, Baltimore, MD, USA.

The Journal of Antimicrobial Chemotherapy
|September 30, 2017
PubMed
Abstract

Insights

Colistin resistance in Klebsiella pneumoniae often involves mgrB gene changes. This study found that lipid A modification with Ara4N is the primary mechanism for colistin resistance in clinical settings.

Area of Science:

  • Microbiology
  • Genetics
  • Biochemistry

Background:

  • Colistin resistance in Klebsiella pneumoniae is a growing concern.
  • Mechanisms typically involve mutations in mgrB, pmrAB, or phoPQ genes.
  • Limited data exists on the resulting modifications to lipopolysaccharide (LPS).

Purpose of the Study:

  • To investigate chromosomal gene sequences linked to colistin resistance.
  • To analyze lipopolysaccharide (LPS)-derived lipid A profiles.
  • To compare 11 pairs of colistin-susceptible and resistant KPC-producing K. pneumoniae clinical strains.

Main Methods:

  • High-throughput sequencing (Illumina HiSeq) for gene analysis.
  • Polymerase Chain Reaction (PCR) and sequencing for mgrB gene.
  • Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) for lipid A profiling.

Main Results:

  • Seven of 11 resistant strains showed mgrB inactivation (deletion or insertion).
  • Three resistant strains exhibited pmrB mutations, with one also having an mgrB deletion.
  • All resistant strains displayed lipid A modification with 4-amino-4-deoxy-l-arabinose (Ara4N), unlike most susceptible strains.

Conclusions:

  • Lipid A modification with Ara4N is the predominant pathway to colistin resistance in Klebsiella pneumoniae.
  • This modification is crucial in clinical settings for developing resistance.
  • Understanding this mechanism aids in combating antibiotic resistance.

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