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Background: Antimicrobial resistance of Salmonella enterica is a major global concern. Recent findings suggest that colistin as a last resort treatment for multidrug-resistant gram-negative bacteria is seriously threatened by the report of plasmid-mediated colistin resistance gene mcr-1 in China. Methods: A total of 827 S. Typhimurium isolates were recovered from 4 cities of China, including Henan, Shanghai, Zhejiang, and Hubei provinces. Subsequently, mcr-1 presence was identified by PCR screening. Antimicrobial susceptibility testing was performed by broth microdilution using a 96-well microtiter plate. Plasmid conjugation transfer experiments were conducted using Escherichia coli J53 as the recipient. Results: Only one mcr-1 positive strain from the stool sample of an infant with acute diarrhea was isolated. Apart from colistin, the mcr-1-positive isolate showed co-resistance to the third-generation cephalosporins, ampicillin, nalidixic acid, tetracycline, chloramphenicol, sulfisoxazole, gentamicin, and cefotaxime revealing a multidrug-resistant phenotype. This strain harbored mcr-1 on a 227 kb IncHI2 plasmid, termed pJZ26, which could be transferred to E. coli J53. In addition to mcr-1, pJZ26 coharbored other resistance genes, including aph(4)-Ia, aac(3)-IVa, fosA, floR, sul2, and blaCTX-M-14. Compared with p2474-MCR1 and pHYEC7-IncHI2, pJZ26 contains an additional 4.6 kb fragment harboring the resistance gene tet(A) and its regulator tetR located on TnAs1 transposable element, which could mediate resistance to tetracycline. Conclusions: These findings highlight that the fact the mcr-1–harboring plasmid pJZ26 has a high potential to disseminate the mcr-1 gene and further challenge the clinical treatment.