Genomic characterization of antimicrobial resistance and virulence determinants in Salmonella Infantis isolated from human, food, and animal sources

ABSTRACT Salmonella Infantis has emerged as a significant cause of foodborne illness, largely due to its increasing antimicrobial resistance (AMR) and capacity to cause widespread disease. A key contributor to its emergence is the acquisition of the pESI plasmid, which harbors multiple virulence genes and resistance determinants to multiple antimicrobial classes. This enhances the spread of multidrug-resistant strains, complicating treatment and increasing infection risks. To understand the genetic factors contributing to the growing prevalence of S . Infantis, whole genome sequencing (WGS) of 15,806 isolates from various sources was analyzed. WGS data extracted from GenBank and EnteroBase were assessed for their putative virulence genes and plasmid transfer genes using the Virulence and Plasmid Transfer Factor Database. Metadata and AMR gene profiles were extracted from the NCBI Pathogen Detection Isolate Browser or analyzed using AMRFinderPlus when unavailable in NCBI. A total of 153 distinct AMR genes were detected, with 68.24% ( N = 10,786) of the isolates carrying at least one AMR gene. The most observed resistance genes included tet(A) ( N = 9,385; 59.38%), sul1 ( N = 9,177; 58.06%), aadA1 ( N = 9,026; 57.10%). Notably, 66.27% ( N = 10,474) of isolates carried at least one transfer gene associated with IncI1. The six pESI plasmids examined in this study contained all IncI1-related transfer genes except IncI1_pilI and IncI1_traD , which suggested the possible recombination or mosaicism between IncI1- and pESI-like elements. Moreover, most of the isolates (87.45%; N = 13,822) shared a common virulence gene profile containing 435 out of the 594 putative virulence genes examined, with only minor variations among the remaining isolates. The considerable overlap in virulence genes, AMR genes, and plasmid transfer gene profiles between human isolates and those from other sources implies potential links between foodborne contamination and human infections. IMPORTANCE This study provides a comprehensive genomic analysis of over 15,000 Salmonella Infantis isolates, revealing widespread antimicrobial resistance (AMR), virulence gene prevalence, and plasmid transfer potential. The high frequency of key AMR genes and the detection of chimeric plasmids highlight the evolving threat posed by multidrug-resistant S. Infantis. The strong similarity in virulence gene profiles between human and non-human isolates underscores the potential for zoonotic transmission through the food chain. These findings offer crucial insights into the mechanisms driving the emergence and spread of resistant S. Infantis, informing future surveillance, risk assessment, and control strategies to protect public health.