Molecular Characterization of Pandrug-,Extensively Drug-,and Multidrug-Resistant Stenotrophomonas maltophilia Isolates from Thailand

Abstract

Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen associated with severe hospital-acquired infections. The multiple drug-resistant nature of S. maltophilia poses significant challenges in treating infections caused by it. In this study, genomic, antimicrobial susceptibility, and virulence phenotypic analyses of four S. maltophilia clinical isolates—strains SMC1291, SMC3920, SMC5345, and SMC5580—were conducted. Comparative genome analysis of these strains against publicly available clinical and environmental isolates revealed its relativeness and key antimicrobial resistance mechanisms. A phylogenetic tree revealed that S. maltophilia SMC5345 is closely related to SMC3920, whereas SMC5580 is closely related to Stenotrophomonas sepilia—the S. maltophilia complex. SMC1291 exhibited resistance to trimethoprim–sulfamethoxazole and gentamicin due to the acquisition of the antibiotic resistance genes sul1 and aac(6’)-Ib, resulting in an extensively drug-resistant strain. SMC3920 showed resistance to trimethoprim–sulfamethoxazole and quaternary ammonium compounds, arising from the acquisition of antimicrobial resistance genes sul1 and qacF. SMC3920 also demonstrated resistance to levofloxacin and minocycline, which was attributed to the L116Q amino acid substitution in SmeT. The combined acquisition of antimicrobial resistance genes and a chromosomal mutation rendered strain SMC3920 resistant to all clinically relevant antibiotics, classifying it as a pandrug-resistant (PDR) strain. Notably, sul1, aac(6’)-Ib, and qacF were encoded within the mobile genetic element class 1 integron. The effects of sul1 and qacF upon gene transfer were studied, corroborating their contribution to the antimicrobial resistance phenotype. Even though the PDR strain SMC3920 remained susceptible to aztreonam and ceftazidime/avibactam combination, exploration of novel therapeutic strategies is urgently needed to combat these difficult-to-treat S. maltophilia infections.