Coexistence of Multidrug Resistance and Hypervirulence-Associated Genes in Clinical Carbapenem-Resistant Pseudomonas aeruginosa

Abstract

The recent worldwide emergence of hypervirulent, multidrug-resistant Pseudomonas aeruginosa represents a critical public health threat. The molecular typing, multidrug resistance (MDR) rates, and hypervirulence-associated genes in carbapenem-resistant P. aeruginosa (CRPA) isolates can vary across geographic locations and patients, highlighting their clinical significance. In this study we investigated the epidemiology and relationship between MDR and the presence of hypervirulenceassociated genes in CRPA isolates. Accordingly, we performed antimicrobial susceptibility tests, multilocus sequence typing (MLST), and PCR-based detection of carbapenemase and virulenceassociated genes. Notably, 34.9% (139/398) of the isolates were carbapenem-resistant, with 79.1% of these exhibiting MDR. Of the 30 sequence types (STs) identified by MLST, ST773 was the most prevalent (28.8%), followed by ST235 (23.0%). New Delhi metallo-β-lactamase (NDM)-1 or imipenemase6 occurred in 45.3% of the CRPA strains. Common virulence genes included exoT (100.0% of isolates), exoY (95.7%), exoU (66.2%), and exoS (34.5%). exoU was associated with antibiotic resistance (p < 0.05), except for carbapenems in CRPA isolates. The exoU/exoT/exoY Type III secretion system (T3SS) genotype was the most prevalent among the carbapenemase-producing CRPA strains. Among the 139 CRPA isolates, we identified a pandrug-resistant, NDM-1-producing ST235 strain co-expressing exoS and exoU. This study highlights the important association between exoU and MDR, indicating a potential relationship between T3SS genotypes and antibiotic resistance. Additionally, the identification of a hypervirulent, pandrug-resistant P. aeruginosa ST235 isolate harboring blaIMP-6 underscores the critical need for enhanced surveillance against high-risk strains.