Genomic characterization of a virulent multidrug-resistant Salmonella enterica serovar Enteritidis strain isolated from meat rabbits (Oryctolagus cuniculus) in China.

Abstract

BACKGROUND: Salmonella enterica serovar Enteritidis (SE) is a major foodborne pathogen. While poultry is a known source, the threat from other livestock like rabbits (Oryctolagus cuniculus) is not well studied. This work investigates a highly virulent, multidrug-resistant (MDR) SE isolate, SE JL228, from a lethal rabbit farm outbreak in China in 2018. The objective of this study was to elucidate the genetic characteristics, antimicrobial resistance determinants, metal tolerance mechanisms, and virulence potential of a rabbit-derived isolate. This study provides important insights that advance our understanding of public and animal health risks. RESULTS: This isolate exhibited resistance to 13 antibiotics within 8 antimicrobial categories as well as to silver (Ag), copper (Cu), and tellurium (Te). Additionally, SE JL228 demonstrated high tolerance to the quaternary ammonium compound (QAC) disinfectant. In vitro, it strongly invaded human brain endothelial cells (hBMECs) and survived longer inside macrophages than the moderately virulent SE strain LN248. In vivo studies confirmed extensive dissemination in mice, with an LDapproximately 68-fold lower than that of LN248. A 4.7-megabase chromosome together with two plasmids-pSE228A (211.4 kb, IncFIB/IncHI2) and pSE228B (54.6 kb, IncN)-was identified through whole-genome sequencing. The genome encoded 17 antibiotic resistance genes (ARGs), 34 virulence factors, heavy metal resistance operons (copESDBAC, silPABFCRE, terEDCBAZWYX), and QAC-resistance gene (qacE) on pSE228A. The plasmid pSE228A shares near-identical structure with a previously-isolated IncHI2 plasmid. The plasmid pSE228B harbors the transferable blaTEM-1B gene responsible for penicillin resistance. CONCLUSIONS: The rabbit-derived SE JL228 represents a highly virulent, MDR, and metal-tolerant pathogen. Its ability to invade hBMECs, survive within macrophages, and disseminate systemically underscores its zoonotic potential. Transferable plasmids combining resistance and virulence determinants suggest an increased risk of dissemination within farm environments and beyond. These findings emphasize the urgent need for enhanced surveillance, prudent antimicrobial use, and effective biosecurity measures to mitigate the emergence and dissemination of such hybrid pathogens.