Regional surveillance of non-A-F Salmonella enterica reveals diverse risk profiles, with global genomic insights from Salmonella Worthington.

Non-A-F Salmonella enterica serovars have received limited attention in public health surveillance, although accumulating evidence suggests that some members of this group may contribute to foodborne illness and infectious diarrhea. To better understand their epidemiological and clinical relevance, we analyzed 2375 S. enterica isolates collected from food products and human diarrheal cases in Wenzhou, China (2014-2024). Although relatively uncommon, a total of 11 distinct non-A-F serovars were identified in our regional dataset; these serovars affected both children and older adults and showed heterogeneous in predicted virulence determinants and antimicrobial resistance profiles. Several serovars displayed unexpectedly high invasive potential or carried substantial resistance gene burdens. Among these serovars, S. Worthington was selected as a representative example for further investigation due to its repeated detection in regional surveillance and the limited genomic information currently available. Global phylogenomics of 742 S. Worthington genomes uncovered four major lineages and suggested a complex evolutionary and dissemination history shaped by sampling diversity, with multiple international transmission events observed. Together, these findings suggest that neglected non-A-F serovars may represent underrecognized public health risks, with S. Worthington illustrating how individual serovars within this group can combine multidrug resistance with broad geographic dissemination. Our work highlights the need to strengthen surveillance of selected non-A-F serovars and to incorporate genomic monitoring of high-risk lineages within a One Health framework.