Data Sheet 1_Genomic dissection of the antimicrobial resistance epidemiology of Salmonella Typhimurium.csv

IntroductionSalmonella Typhimurium (STm) is a globally distributed foodborne pathogen showing increasing antimicrobial resistance (AMR), particularly to fluoroquinolones and third-generation cephalosporins. Multiple countries have implemented ongoing genomic surveillance programs for Salmonella, but comprehensive global analyses integrating genomic typing and AMR in STm remain scarce.
MethodsPublicly available genomes of ~65,000 STm isolates were characterized using Multilevel Genome Typing (MGT). Resistance was predicted to 14 clinically-relevant antibiotics. Resistance patterns were analyzed by MGT sequence type (ST), geographic location, year of collection, and source. MGT ST where ≥80% isolates were predicted to be resistant to an antibiotic were defined as a resistant ST for that antibiotic.
ResultsAbout half of all STm isolates were predicted to be resistant to ≥1 antibiotic. Resistance frequencies varied substantially by country, collection year and MGT ST, and 407 resistant MGT STs were identified. Among the most recent isolates (2021–2022), eight MGT STs were classified as cefotaxime resistant and three as ciprofloxacin intermediate. Cefotaxime resistant MGT STs predominantly included isolates from cattle/poultry in the USA. Ciprofloxacin intermediate MGT STs were mainly linked to swine from the UK.
DiscussionThis large-scale genomic analysis highlights substantial diversity in AMR patterns among STm genomic types globally. The identification of recently emerged cefotaxime resistant and ciprofloxacin intermediate STs underscores the continued threat of resistance to antibiotics critical for treatment of severe salmonellosis. Integration of MGT strain typing with AMR prediction provides scalable, sharable, standardised and precise tracking of resistant isolates/STs, offering a powerful framework for global AMR surveillance.

引言：鼠伤寒沙门氏菌（Salmonella Typhimurium, STm）是一种全球分布的食源性致病菌，其抗菌药物耐药性（antimicrobial resistance, AMR）呈上升趋势，尤其对氟喹诺酮类和第三代头孢菌素类药物耐药情况突出。目前多个国家已针对沙门氏菌启动持续的基因组监测计划，但针对STm整合基因组分型与耐药性分析的全球性综合研究仍较为匮乏。
方法：本研究采用多级基因分型（Multilevel Genome Typing, MGT）对公开获取的约65000株STm分离株的基因组进行解析。针对14种临床相关抗生素进行耐药性预测，并依据MGT序列型（MGT sequence type, ST）、地理位置、分离年份及分离来源对耐药模式展开分析。将某一抗生素对应≥80%分离株被预测为耐药的MGT序列型，定义为该抗生素的耐药序列型。
结果：约半数STm分离株被预测对至少1种抗生素耐药。耐药频率因国家、分离年份及MGT序列型的不同存在显著差异，共鉴定出407个耐药MGT序列型。在2021-2022年的最新分离株中，有8个MGT序列型被归类为头孢噻肟（cefotaxime）耐药型，3个为环丙沙星（ciprofloxacin）中介型。头孢噻肟耐药型MGT序列型的分离株主要来自美国的牛/家禽样本，而环丙沙星中介型MGT序列型则主要与英国的猪源分离株相关。
讨论：本次大规模基因组分析揭示了全球范围内STm基因组分型中抗菌药物耐药模式的显著多样性。本次鉴定出的新近出现的头孢噻肟耐药型与环丙沙星中介型序列型，进一步凸显了重症沙门氏菌病治疗关键抗生素的耐药性仍持续构成威胁。将MGT菌株分型与耐药性预测相结合，可实现耐药分离株/序列型的可扩展、可共享、标准化且精准的追踪，为全球抗菌药物耐药性监测提供了强有力的研究框架。