Global diversity and Azithromycin resistance of Salmonella enterica serovar London: a genomic epidemiology study

Non-typhoidal Salmonella enterica serovar London (S. London) represents an emerging zoonotic threat with escalating azithromycin resistance, yet its global population structure and evolutionary dynamics remain poorly characterized. Here we present a genomic epidemiology analysis of 946 global isolates from 1984–2024, revealing four major clades (C1–C4) and eight sub-clades, with distinct geographical distributions and host adaptations. Notably, sub-clade C1.1 was predominantly endemic to China, while C3.1 demonstrated cosmopolitan distribution. The C1.1 exhibited alarming azithromycin resistance (62.1%, 123/198) driven by mphA-harboring multidrug resistance cassettes located on IncFIB(K) plasmids. These super-resistance islands, mobilized by transposable elements, facilitate horizontal transmission across animal-food-human interfaces. Distinct sub-clades exhibited specialized virulence–resistance co-evolutionary strategies. Analysis revealed a farm-to-fork transmission trajectory, with pork production systems as the primary conduit for dissemination. Our findings highlight the urgent need for integrated One Health surveillance to contain the global dissemination of high-risk MDR clones and preserve last-resort antimicrobial therapies.