Objective To investigate a cholera outbreak in Luzhou City,China in 2022,and to identify the drug resistance and genomic characteristics of Vibrio cholerae strains.Methods A total of 267 samples were collected from cholera cases,their family members and meal companions,the living environment of these cases,the environment of aquatic products market,aquatic products,and domestic drinking water for V.cholerae isolation and culture.The isolates were subjected to serological typing and cholera toxin gene(ctxAB)identification.Drug susceptibility test was performed according to the guideline of Chi-nese Pathogen Identification Net,and next generation sequencing was used for virulence gene analysis,resistance gene predic-tion,and phylogenetic analysis.Results Seven isolates of V.cholerae serogroup O139 were obtained from the 267 samples,in-cluding one from a case,one from the environment and five from healthy carriers.All the isolates were resistant to polymyxin E,tetracycline,nalidixic acid and streptomycin,but showed intermediate resistance to chloramphenicol.Sequencing revealed that all the isolates carried genes related to resistance to fluoroquinolones,polypeptides,sulfonamides,tetracyclines,β-lactams,macrolides,aminoglycosides and chloramphenicol,as well as virulence genes such as ctxA B and hlyA.All the isolates were ST69 according to multilocus sequence typing analysis and cgST-1314 according to core-genome multilocus sequence typing.The isolate from the case(SC2022LZS511)differed by only four single nucleotide polymorphism sites from the cholera case iso-late from Shaanxi Province in 2022.Conclusion The V.cholerae serogroup O139,which caused this outbreak,was a domes-tically circulating strain that exhibited resistance to a variety of antibiotics and carries multiple resistance and virulence genes.