单相鼠伤寒沙门菌（Salmonella enterica serovar 4,[5],12:i:-, S. 4,[5],12:i:-）作为鼠伤寒沙门菌的变种，已成为全球公共卫生领域备受关注的新兴血清型，其在中国的基因组流行病学特征尚不明确。本研究对2008-2017年分离自腹泻患者的100株序列型34型（ST34）S. 4,[5],12:i:-开展的流行情况、耐药表型和群体基因组学的分析发现：多数菌株对氨苄西林、链霉素、磺胺类和四环素耐药（耐药表型ASSuT）；基于贝叶斯系统发育分析，中国分离株起源于欧洲谱系，进化为携带不同耐药基因和质粒的两个分支。进化支1中gyrA基因点突变和质粒介导喹诺酮耐药基因携带率较高，而进化支2中多数菌株fljBA操纵子插入了耐药编码区域[编码ASSuT耐药表型，包括bla_TEM-1B（氨苄西林耐药）、strAB（链霉素耐药）、sul2（磺胺类耐药）和tet(B)（四环素耐药）]，导致了血清型单相变异。IncHI2质粒是该血清型中导致细菌严重耐药的主要可移动遗传元件，普遍存在于进化支1的分离株中。综上，多重耐药S. 4,[5],12:i:-菌株在中国的流行情况日益严重，且进化为携带不同耐药基因的多个谱系，需采取有效措施控制此人畜共患病原体的传播，并基于'同一健康'策略开展监测及制定干预策略。

Salmonella enterica serovar 4,[5],12:i:- (S. 4,[5],12:i:-) is a monophasic variant of Salmonella enterica serovar Typhimurium that has emerged as a global serovar causing public health concern. To date, the epidemiology and genomic characterization of this pathogen in China have not been well described. We investigated the prevalence, antimicrobial resistance (AMR) phenotypes, and population genomics of sequence type 34 (ST34) S. 4,[5],12:i:- among cases of human salmonellosis in Henan Province, China. A total of 100 ST34 S. 4,[5],12:i:- isolates were studied from 2008 to 2017 and found mostly resistant to ampicillin (AMP), streptomycin (STR), sulfonamides (SUL), and tetracycline (TET) (ASSuT). Bayesian phylogenetic analysis demonstrated that isolates identified in China were mostly related to the European lineage and evolved into two major clades with different resistance genes and plasmid profiles. Notably, clade 1 showed a significantly higher rate of mutations in gyrA and plasmid-mediated quinolone resistance genes. The carrying of the resistance-containing region (encoding R-type ASSuT), including bla_TEM-1B (conferring resistance to AMP), strAB (STR), sul2 (SUL), and tet(B) (TET) inserted into the fljBA operon, was responsible for most of the monophasic variants in clade 2. IncHI2 plasmids were the dominant multi-drug resistance mobile genetic elements accounting for the transmission of acquired resistance genes in this serovar, and these were more prevalent in clade 1. Our findings highlighted the increasing prevalence of multi-drug resistant S. 4,[5],12:i:- in China, along with the differential characteristics of resistance gene acquisition among various lineages. Based on our data, control measures are required to address the spread of this zoonotic pathogen. Further owing to its potential origin in food-producing animals, a ″One Health″ approach, should be implemented to support surveillance whilst informing interventional strategies.