Prevalence and dissemination of mcr-9.1 -producing non-typhoidal Salmonella strains from diarrhea patients throughout China during 2010–2020

The emergence of mobilized colistin resistance ( mcr ) genes has raised significant concerns as they pose a public health issue. The prevalence of mcr genes, particularly the newly discovered mcr-9 gene, in non-typhoidal Salmonella (NTS) isolates remains unclear. We characterized mcr-9.1 -producing NTS isolates from China. Among 7,106 NTS isolates from diarrhea cases in 32 provinces during 2010–2020, 11 mcr-9.1 -producing isolates were identified and were all not resistant to colistin. Five isolates belonged to Salmonella Thompson and sequence type (ST) 26, two belonged to Salmonella Typhimurium and ST34, two belonged to Salmonella Typhimurium and ST36, and two belonged to Salmonella 1,4,[5],12:i:- and ST34. Plasmids harboring mcr-9.1 tended to possess the IncHI2 backbone and were ~ 300 kb long. All mcr-9.1 genes shared the same flanking sequence, rcnR-rcnA - pcoS -IS 903 - mcr-9.1 - wbuC . According to the NCBI data, we found that NTS serves as the primary host of mcr-9.1 , although the prevalence of specific serotypes differed between domestic and international settings. Notably, most data came from developed countries, such as the USA. mcr-9.1 tended to be transferred as a gene cassette or to be mobilized by a conjugational plasmid in multiple bacteria across humans, animals, and the environment. Furthermore, mcr-9.1 frequently co-existed and was co-transferred with various genes encoding resistance to first-line drugs, reducing the effectiveness of available therapeutic options. In summary, although mcr-9 does not mediate colistin resistance, it can silently spread with some genes encoding resistance to first-line drugs, and therefore warrants research attention.