Novel Class 1 Integron Structures in High-Risk Metallo-β-Lactamase-Producing Pseudomonas aeruginosa ST235 and ST654 From Companion Animals.

Abstract

INTRODUCTION: Carbapenemase-producing Pseudomonas aeruginosa (CP-Pa) has emerged as a significant clinical and public health concern due to its ability to limit treatment options with last-resort antimicrobials. This study aims to characterise novel class 1 integron (Int1) structures containing blaand blain high-risk CP-Pa sequence type (ST) 235 and ST654 strains from dogs and cats and illustrate the genetic relatedness between CP-Pa strains from animal and human origins. METHODS AND RESULTS: Of the four CP-Pa strains, whole-genome sequencing and analysis revealed that three strains belonged to ST235/O11/exoU+/exoS-, with two strains harbouring bla, and one strain harbouring bla. The remaining strain was characterised as ST654/O4/exoU-/exoS+ and harboured bla. Core-genome single nucleotide polymorphism-based phylogeny illustrated genetic relationships between animal and human high-risk CP-Pa ST235/O11 and ST654/O4 strains within the same STs. Three novel Int1 gene cassette arrays were identified in the canine and feline CP-Pa strains in this study. The novel ~6.2-kb bla-containing Int1[Pae-CUVET21-397] and Int1[Pae-CUVET23-830] (intI1-aadB-bla-aadB-cmlA6-qacE∆1-folP) formed a complex Int1 located in an integrative and conjugative element of two feline CP-Pa ST235 strains. The canine CP-Pa ST235 strain CUVET20-956 contained a novel ~5.8-kb bla-containing Int1[Pae-CUVET20-956] (intI1-bla-aacA4-aacA4-IS1595-qacE∆1-sul1). The CP-Pa ST654 strain CUVET18-860 contained In1206 encoding blaand a novel ~5.9-kb Int1[Pae-CUVET18-860] (∆intI1-bla-aadB-qnrVC1-aacA4-bla-aadA1-dfrA14) encoding multidrug resistance (MDR). Additionally, In51-containing Tn6162 inserted in genomic island 1 was identified in all CP-Pa ST235 strains. CONCLUSIONS: The novel Int1s encoding metallo-β-lactamases and MDR in canine and feline CP-Pa play a crucial role in the development of resistance to multiple antimicrobials and last-resort carbapenems in P. aeruginosa ST235 and ST654 strains of veterinary and public health importance, posing possible zoonotic and anthroponotic transmission of the high-risk CP-Pa clones between companion animals and humans.