Global prevalence and distribution of bla-harboring Salmonella: A genome-wide association study of cephalosporin resistance mechanisms.

Given the increasing global concern over Salmonella resistance to cephalosporins, such resistance poses serious challenges to food safety and clinical treatment. This study aimed to systematically investigate the global epidemiological characteristics and genetic diversity of bla-harboring Salmonella to further elucidate the association between bla genes and cephalosporin resistance phenotypes. A total of 772,454 Salmonella isolates from the NCBI Pathogen Detection database were analyzed, among which 101,448 isolates harbored bla genes. Most isolates originated from humans, poultry, and pigs, mainly in North America, Europe, and Asia. The dominant serovars were S. 4,[5],12:i: , S. Typhimurium, S. Infantis, and S. Enteritidis. The most frequent β-lactamase families were blaTEM, blaCMY, and blaCTX-M, with blaTEM-1, blaCMY-2, and blaCTX-M-65 as the predominant subtypes. To further elucidate the correlation between bla genotype and cephalosporin resistance phenotype, we assessed cephalosporin susceptibility of 2302 Salmonella isolates collected in China. Resistance testing showed ceftriaxone and cefoxitin resistance rates were of 20.68% and 5.82%, respectively, with higher resistance rate observed in chicken isolates than in pork isolates. Twenty-two bla genes were detected, mainly blaTEM-1B, blaOXA-1, and blaCTX-M-65. Correlation and regression analyses indicated that ceftriaxone resistance was primarily driven by CTX-M-type ESBLs, while cefoxitin resistance was linked to blaDHA-1 and blaCMY-2. Machine learning models effectively predicted cephalosporin susceptibility. Genome-wide association study (GWAS) identified multiple functional categories associated with ceftriaxone resistance, including those related to amino acid, carbohydrate, and inorganic ion transport and metabolism, as well as secondary metabolite biosynthesis and catabolism.