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In December 2021, a wildlife conservation base in Hunan, China, reported illness and death among its captive Myocastor coypus population. A gram-positive pathogen was isolated from the affected animals. The 16S rDNA sequence of the isolated strain was approximately 1,500 bp long and exhibited 98.4% homogeneity with Staphylococcus cohnii found in sea cucumbers. Interestingly, the biochemical reactions of the isolated strain were consistent with the characteristics of S. cohnii. The LD100 for BALB/c mice was 1.2 × 107 CFU/g, while the MLD was 0.6 × 107 CFU/g. Inflammatory cell infiltration was observed in the liver, spleen, and kidneys of infected mice, accompanied by widespread systemic bacteremia and focal hepatic and splenic necrosis. Moreover, mycelium was detected in the liver and kidney. The isolated strain possessed both HLB and PVL virulence genes. To the best of our knowledge, this is the first study to report a highly pathogenic strain of S. cohnii isolated from M. coypus, possessing both HLB and PVL virulence genes. The findings contribute to yielding a better understanding of the pathogenic mechanisms of S. cohnii and have significant implications for disease control in M. coypus, as well as for public health safety and the prevention of zoonotic diseases. [ABSTRACT FROM AUTHOR]