Emergence of ST463 exoU-Positive, Imipenem-Nonsusceptible Pseudomonas aeruginosa Isolates in China

Microbiol Spectr. 2023 Aug 17;11(4):e0010523. doi: 10.1128/spectrum.00105-23. Epub 2023 Jun 14.

Abstract

This study investigated the resistance mechanisms and the distribution and proportions of virulence genes, including exoU, in 182 imipenem-nonsusceptible Pseudomonas aeruginosa (INS-PA) strains collected from China in 2019. There was no obvious prevalent sequence type or concentrated evolutionary multilocus sequence typing (MLST) type on the INS-PA phylogenetic tree in China. All of the INS-PA isolates harbored β-lactamases with/without other antimicrobial mechanisms, such as gross disruption of oprD and overexpression of efflux genes. Compared with exoU-negative isolates, exoU-positive isolates (25.3%, 46/182) presented higher virulence in A549 cell cytotoxicity assays. The southeast region of China had the highest proportion (52.2%, 24/46) of exoU-positive strains. The most frequent exoU-positive strains belonged to sequence type 463 (ST463) (23.9%, 11/46) and presented multiple resistance mechanisms and higher virulence in the Galleria mellonella infection model. The complex resistance mechanisms in INS-PA and the emergence of ST463 exoU-positive, multidrug-resistant P. aeruginosa strains in southeast China indicated a challenge that might lead to clinical treatment failure and higher mortality. IMPORTANCE This study investigates the resistance mechanisms and distribution and proportions of virulence genes of imipenem-nonsusceptible Pseudomonas aeruginosa (INS-PA) isolates in China in 2019. Harboring PDC and OXA-50-like genes is discovered as the most prevalent resistance mechanism in INS-PA, and the virulence of exoU-positive INS-PA isolates was significantly higher than that of exoU-negative INS-PA isolates. There was an emergence of ST463 exoU-positive INS-PA isolates in Zhejiang, China, most of which presented multidrug resistance and hypervirulence.

Keywords: Pseudomonas aeruginosa; ST463; exoU; imipenem nonsusceptible; resistance mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Humans
  • Imipenem* / pharmacology
  • Imipenem* / therapeutic use
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Phylogeny
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas aeruginosa
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Imipenem
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases