Comprehensive analysis of β-lactam resistant non-typhoidal Salmonella Isolates: Phenotypic and genotypic insights from clinical samples in Japan

Objective: This study examines β-lactam-resistant non-typhoidal Salmonella isolates using phenotypic and genotypic analyses to elucidate resistance mechanisms and epidemiological characteristics. Methods: A total of 1663 clinical Salmonella spp. isolates were collected (1994–2016), with 122 exhibiting β-lactam resistance, confirmed via antimicrobial susceptibility testing. Resistance mechanisms were further explored through genotypic analysis by whole genome sequencing, plasmid characterization, and phylogenomic investigations. Results: All isolates were resistant to at least one β-lactam. Resistance to third-generation cephalosporins was notable, while carbapenem resistance was rare (0.8%). High resistance was observed for minocycline (36.9%) and sulfamethoxazole-trimethoprim (28.7%), whereas resistance to fluoroquinolones (3.3%–5.7%), aminoglycosides (0.8%–8.2%), and tigecycline (8.2%) was low. All isolates remained susceptible to fosfomycin, and 21.3% exhibited multidrug resistance. Genotypic analysis identified diverse serotypes and sequence types, with S. Typhimurium and ST19 being predominant. The most common β-lactamase gene was bla_TEM, followed by bla_CARB-2, with significant correlations between β-lactam and aminoglycoside resistance genes. Plasmid analysis revealed a high prevalence of plasmid carriage, with IncFII(S) and IncFIB(S) being predominant, strongly associated with antimicrobial resistance genes. Phylogenetic analysis provided insights into the global dissemination of Salmonella, particularly those carrying mcr-9, while clustering analysis revealed shared genetic patterns among isolates sourced from different hosts, highlighting the potential for cross-species transmission. Conclusions: These findings underscore the complex interplay of resistance mechanisms and emphasize the need for integrated surveillance and intervention strategies to combat antimicrobial resistance in Salmonella, reinforcing the necessity for ongoing public health efforts.