Genomic insights into ceftazidime resistance in Burkholderia pseudomallei: discovery of A172T mutation and palindromic GC-rich repeat sequences facilitating penA duplication and amplification

Antimicrob Agents Chemother. 2025 Aug 6;69(8):e0022025. doi: 10.1128/aac.00220-25. Epub 2025 Jul 21.

Abstract

Ceftazidime (CAZ) resistance in Burkholderia pseudomallei, the causative agent of melioidosis, complicates treatment in endemic regions. This study identified a novel A172T mutation and other known penA mutations as critical contributors to CAZ resistance in a large Thai strain collection. Frequent gene duplication and amplification of penA, likely driven by Palindromic GC-Rich Repeat Sequences, highlights the urgent need for rapid diagnostics and optimized treatment strategies to manage this life-threatening disease effectively.

Keywords: AMR; Burkholderia pseudomallei; ceftazidime; melioidosis; penA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Bacterial Proteins* / genetics
  • Burkholderia pseudomallei* / drug effects
  • Burkholderia pseudomallei* / genetics
  • Ceftazidime* / pharmacology
  • Drug Resistance, Bacterial* / genetics
  • Gene Duplication
  • Humans
  • Inverted Repeat Sequences / genetics
  • Melioidosis / drug therapy
  • Melioidosis / microbiology
  • Microbial Sensitivity Tests
  • Mutation / genetics

Substances

  • Ceftazidime
  • Anti-Bacterial Agents
  • Bacterial Proteins