Comparative genomics of colistin-nonsusceptible multidrug-resistant Pseudomonas aeruginosa reveals emerging lineages in Thailand

Abstract

Pseudomonas aeruginosa is a leading cause of multidrug-resistant (MDR) infections, for which the polymyxin antibiotic colistin has been a treatment of last resort. The emergence of colistin-nonsusceptible strains thus poses a serious therapeutic challenge. In this study, we performed whole-genome sequencing and comparative genomic analysis of 29 colistin-nonsusceptible MDR P. aeruginosa clinical isolates collected from hospitals across Thailand between 2021 and 2022. The genomic analysis identified nine distinct sequence types (STs), including a previously uncharacterized ST (ST5340) closely related to the high-risk international clone ST357. This novel ST was the most prevalent (24%) and all of its isolates exhibited resistance to all tested antibiotics. Comprehensive resistome profiling revealed widespread possession of resistance determinants, including multiple beta-lactamases (e.g., bla<inf>NDM-1</inf>, bla<inf>OXA-10-like</inf>, bla<inf>OXA-10</inf>, bla<inf>OXA-846</inf> and bla<inf>VEB</inf>), aminoglycoside-modifying enzymes, and colistin resistance-associated mutations. SNP-based phylogenetic analysis of 108 Thai P. aeruginosa genomes, including 79 in a public database and those of the 29 newly sequenced isolates, revealed dominant clusters formed by ST5340, ST357, ST654, and ST235. The widespread distribution of ST5340 across multiple regions of Thailand suggests its emergence as a potential epidemic high-risk clone. These findings highlight the genetic diversity and geographical spread of colistin-nonsusceptible P. aeruginosa in Thailand. The emergence of ST5340 as a dominant, extensively drug-resistant lineage underscores the urgent need for continued genomic surveillance to inform infection control and antimicrobial stewardship efforts.