摘要目的:了解杭州地区临床和食品来源鼠伤寒沙门菌及其单相变种的耐药特征，并进行基因组分析。方法:对2017—2021年杭州地区分离的78株鼠伤寒沙门菌及108株鼠伤寒沙门菌单相变种进行药敏分析和全基因组测序，下载公共数据库基因组数据；利用测序数据对菌株进行多位点序列分型和耐药基因扫描，并构建基于单核苷酸多态性位点的系统发育树。结果:杭州地区鼠伤寒沙门菌单相变种中同时携带≥3类耐药基因的多重耐药(multidrug resistance, MDR)菌占95.4%(103/108)，其最常见的耐药基因型为 blaTEM-1B- tet( B)- sul2- aac(6′)- Iaa (44.7%, 46/103)，鼠伤寒沙门菌中同时携带≥3类耐药基因的MDR菌占75.6%(59/78)，其中52.5%(31/59)的MDR菌同时携带≥10种耐药基因，最常见的耐药基因型为 blaTEM-1B- qnrS1- tet( A)- tet( M)- cmlA1- floR- dfrA12- sul2- sul3- aac(6′)- Iaa(40.7%, 24/59)；所有186株菌均检出氨基糖苷乙酰转移酶基因 aac(6′)- Iaa，3株单相变种检出 mcr-1.1基因且多黏菌素E耐药；78株鼠伤寒沙门菌除2株为ST34、2株为ST1544、3株未分型外，其余均为ST19型，108株单相变种除4株未分型外，其余均为ST34型；基于397株鼠伤寒沙门菌及其单相变种(包括186株杭州菌株和211株公共数据库菌株)单核苷酸多态性位点构建的系统发育树显示：以鼠伤寒血清型为主的ST19型和以单相变种为主的ST34型菌株分成两个独立的支系；ST19支系中与杭州菌株聚集成簇的主要是分离自浙江省其他地市和江西、上海、山东等国内其他省市的菌株，与临床株聚集成簇的主要是猪、鸭和鸡源分离株；ST34支系中杭州菌株以自行聚集成簇为主，与杭州菌株聚集成簇的主要是分离自浙江省其他地市和北京、广东、上海等地的菌株，与临床株聚集成簇的主要是猪和鸡源分离株。 结论:鼠伤寒沙门菌单相变种的MDR率高于鼠伤寒血清型，但后者的多耐药基因携带不容忽视；杭州地区鼠伤寒沙门菌及其单相变种的流行主要分别由ST19型、ST34型引起，可能跟猪肉和禽肉的消费密切相关，在本地传播的同时，主要与浙江省其他地市和境内其他省市存在跨地传播的可能性。

abstractsObjective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella typhimurium and its monophasic variants isolated from human and food sources in Hangzhou. Methods:A total of 186 Salmonella typhimurium and its monophasic variants isolated in Hangzhou during the period from 2017 to 2021 were subjected to antimicrobial susceptibility testing and whole-genome sequencing, and the genomes from public databases were downloaded. Multilocus sequence typing and the identification of antimicrobial resistance (AMR) genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the genomes from Hangzhou and public databases was constructed. Results:The multidrug resistance (MDR) rate of the monophasic variant strains in Hangzhou was 95.4% (103/108). The MDR strains harbored ≥3 classes of AMR genes simultaneously and the most common resistance genotype was blaTEM-1B- tet( B)- sul2- aac(6′)- Ia (44.7%, 46/103). The MDR rate of Salmonella typhimurium strains was 75.6% (59/78), and 52.5% (31/59) of the MDR strains harbored ≥10 AMR genes simultaneously, with the most common resistance genotype being blaTEM-1B- qnrS1- tet( A)- tet( M)- cmlA1- floR- dfrA12- sul2- sul3- aac(6′)- Iaa (40.7%, 24/59). All of the 186 strains were positive for AMR gene aac (6 ′)- Iaa, and three monophasic variant strains which were resistant to polymyxin E was positive for mcr-1.1. ST19 accounted for 91.0% of the 78 Salmonella typhimurium strains (except for two strains belonging to ST34, two strains belonging to ST1544, and three strains untyped), and ST34 accounted for 96.3% of the 108 monophasic variant strains (except for four strains untyped). The phylogenetic tree showed that the ST19 strains dominated by serotype typhimurium and the ST34 strains dominated by monophasic variants were divided into two clades. In the ST19 clade, strains from Hangzhou were mainly clustered with the strains from other cities in Zhejiang Province as well as other provinces and cities in China, such as Jiangxi, Shanghai, and Shandong. Strains isolated from pig, duck, and chicken were the ones that were clustered with clinical strains. In the ST34 clade, most strains from Hangzhou were clustered together, and some strains were clustered with those isolated from other cities in Zhejiang Province as well as Beijing, Guangdong, Shanghai, etc. Strains isolated from pig and chicken were the ones that were clustered with clinical strains. Conclusions:The MDR rate of monophasic variant strains is higher than that of Salmonella typhimurium strains, and the latter is prominent by its harboring multiple AMR genes. The epidemic of Salmonella typhimurium and its monophasic variants in Hangzhou is mainly caused by the spread of ST19 and ST34 strains, respectively, and the clinical infection may be closely related to the consumption of pork and poultry meat. While transmitting locally, cross-region transmission of the two serovars in Zhejiang Province and cross-province transmission in China may also occur.