The epidemiologic and genomic insights on mcr-1-harbouring Salmonella presents the potential threat in enteric infection and food safety

　　Polymyxins are used as the last-resort antibiotics in the treatment of infections caused by multidrug-resistant Gram-negative bacteria. In early 2016, a new mechanism of colistin resistance, mediated by the transferrable mcr-1 gene, was reported from the Enterobacteriaceae from the farming animals and clinics. Plasmid-mediated mcr-1 gene can spread rapidly among strains, resulting in the spread of colistin resistance.

　　Salmonella is the leading cause of the food-borne disease and food safety issue, can cause serious disease burden in both developed and developing countries. However, understanding on the prevalence and dissemination of mcr-1-positive Salmonella is still limited based on the systematic clinical surveillance in large-scale population. A research team composed of National Institute of Communicable Disease Control and Prevention from China CDC, Shanghai Municipal CDC and other institutions, performed a retrospective study based on a 11-year laboratory-based Salmonellosis surveillance in Shanghai, to determine the prevalence and transmission trend of the mcr-1-harbouring Salmonella in community-acquired infections.

　　From 12,053 Salmonella strains of 108 serotypes isolated in the laboratory-based surveillance started from 2006, 37 strains with mcr-1¬-harboring plasmids were identified. The mcr-1-harboring Salmonella strain was first detected in 2012, and rapidly increased after 2015. Though the totally positive rate of mcr-1 Salmonella strains were low in this study, the explosive increase occurring after 2015, warning that the threat of expansion in the community of Salmonella with mcr-1-mediated colistin resistance in recent years. This laboratory-based Salmonella surveillance covered all age groups of outpatients; however, 90% (33/37) of outpatients suffering from infection with mcr-1-harboring Salmonella were children aged <5 years. Notably, 26 of the 33 mcr-1-positive strains simultaneously carried extended-spectrum β-lactamase (ESBL) genes, which make them resistant to the common antibiotics such as cephalosporins used for the treatment of diarrhea in children. Most mcr-1 strains are also resistant to fluoroquinolone, the commonly used antibiotics in treatment of Salmonella diarrhea. The resistances to these first-choice antibiotics are just like the given wings (ESBL genes and fluoroquinolone resistant genes) to a tiger (mcr-1 gene), as the meaning of a Chinese idiom. Because of the resistance to cephalosporins and fluoroquinolones, these antibiotics used commonly in clinics may unintentionally promote the co-selection and preservation of colistin-resistant Salmonella strains, although colistin is rarely used in the treatment of salmonellosis.

　　This study also found a highly skewed serotype distribution of the mcr-1-positive Salmonella strains; 35 of 37 mcr-1¬-positive strains were serovar Typhimurium. The finding was supported by the results of the mcr-1-harbouring plasmid conjugation experiments conducted in this study, which show that the acquisition of mcr-1 plasmids by S. Typhimurium was ten and seven times higher, respectively, compared with two other common serovars, Enteritidis and Derby.

　　The study also obtained the complete sequences of all 37 mcr-1-harbouring mega-plasmids by short- and long-read sequencing strategies. Therefore, the plasmid structure and resistant genes carried on the plasmids were all clear and facilitated the precise plasmid comparisons. Core-genomic SNP phylogeny combined with mcr-1-harbouring plasmid sequence comparisons revealed genome subtyping clusters, suggesting the presence of mcr-1-harbouring Salmonella outbreaks in the community and that the rapid expansion of colistin-resistant strains in the community presents a potential public health threat. Most mcr-1-positive S. Typhimurium strains (34/35) were clustered together within the swine strain branch in the phylogenetic tree, providing strong genome epidemiology-based evidence that the consumption of pork or the cross-contamination of pork and other foods in food processing is the likely contamination source of mcr-1-harbouring S. Typhimurium. Before 2017, polymyxins were often used as feed additives to prevent animal diseases and promote animal growth, the result highlighted the significance to restrict the use of polymyxins in animal breeding.

　　The findings were reported as “Epidemiologic and genomic insights on mcr-1-harbouring Salmonella from diarrhoeal outpatients in Shanghai, China, 2006–2016” (DOI: https://doi.org/10.1016/j.ebiom.2019.03.006) published in EBioMedicine. Xin Lu (National Institute for Communicable Disease Control and Prevention), Mei Zeng (Children's Hospital of Fudan University), and Jialiang Xu (Beijing Technology and Business University) shared the co-first authors, Xuebin Xu (Shanghai Municipal CDC) and Biao Kan (National Institute for Communicable Disease Control and Prevention) are the co-corresponding authors of this paper.