Increasing prevalence and expanding diversity of tet(X4)-carrying Salmonella in China

The plasmid-mediated tigecycline resistance gene tet(X4) threatens the efficacy of tigecycline. While prevalent in Escherichia coli across diverse ecological niches, its evolutionary trajectory in Salmonella remains underappreciated. Here, we conducted nationwide genomic surveillance of 42403 clinical nontyphoidal Salmonella isolates collected from diarrheal patients in China between 2014 and 2025, of which 102 were tet(X4)-positive. Although the overall prevalence remained low, detection showed a statistically significant upward trend over 2019-2025. Importantly, the newly accrued 2025 data were broadly consistent with short-term forecasts generated by the beta regression model, providing partial support for short-term trend consistency. Genomic analyses showed that tet(X4) remained concentrated in ST34 but was also detected in additional sequence types, including ST469, ST8971, ST11 and one isolate with an unassigned ST, across multiple provinces, indicating broader geographic representation and genetic diversification. Plasmid analyses likewise revealed broader replicon diversity, with the dominant IncHI1A/IncHI1B/IncFIA background accompanied by less frequent IncHI2/IncHI2A, IncI1(Alpha) and IncFIA/IncFIB/IncFIC. Phylogenetic analyses further revealed shared clustering of the dominant plasmid background across host species and bacterial genera, consistent with cross-host and cross-genus circulation. Here, they determine that tet(X4)-carrying Salmonella remains rare in China but is being detected more often and in a wider range of bacterial sequence types and plasmids, supporting continued surveillance.