| Summary: | <i>Salmonella enterica</i> serovar Derby (<i>S</i>. Derby) ranks fifth among nontyphoidal <i>Salmonella</i> serovars causing human infections in the European Union. <i>S</i>. Derby isolates (36) collected between 2006 and 2018 in a Spanish region (Asturias) from human clinical samples (20) as well as from pig carcasses, pork- or pork and beef-derived products, or wild boar (16) were phenotypically characterized with regard to resistance, and 22 (12 derived from humans and 10 from food-related samples) were also subjected to whole genome sequence analysis. The sequenced isolates belonged to ST40, a common <i>S</i>. Derby sequence type, and were positive for SPI-23, a <i>Salmonella</i> pathogenicity island involved in adherence and invasion of the porcine jejune enterocytes. Isolates were either susceptible (30.6%), or resistant to one or more of the 19 antibiotics tested for (69.4%). Resistances to tetracycline [<i>tet</i>(A), <i>tet</i>(B) and <i>tet</i>(C)], streptomycin (<i>aadA2</i>), sulfonamides (<i>sul1</i>), nalidixic acid [<i>gyrA</i> (Asp87 to Asn)] and ampicillin (<i>bla</i><sub>TEM-1</sub>-like) were detected, with frequencies ranging from 8.3% to 66.7%, and were higher in clinical than in food-borne isolates. The <i>fosA7.3</i> gene was present in all sequenced isolates. The most common phenotype was that conferred by the <i>tet</i>(A), <i>aadA2</i> and <i>sul1</i> genes, located within identical or closely related variants of <i>Salmonella</i> Genomic Island 1 (SGI1), where mercury resistance genes were also present. Diverse IncI1-I(α) plasmids belonging to distinct STs provided antibiotic [<i>bla</i><sub>TEM-1</sub>, <i>tet</i>(A) and/or <i>tet</i>(B)] and heavy metal resistance genes (copper and silver), while small pSC101-like plasmids carried <i>tet</i>(C). Regardless of their location, most resistance genes were associated with genetic elements involved in DNA mobility, including a class one integron, multiple insertion sequences and several intact or truncated transposons. By phylogenetic analysis, the isolates were distributed into two distinct clades, both including food-borne and clinical isolates. One of these clades included all SGI1-like positive isolates, which were found in both kinds of samples throughout the entire period of study. Although the frequency of <i>S</i>. Derby in Asturias was very low (0.5% and 3.1% of the total clinical and food isolates of <i>S. enterica</i> recovered along the period of study), it still represents a burden to human health linked to transmission across the food chain. The information generated in the present study can support further epidemiological surveillance aimed to control this zoonotic pathogen.
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