Salmonella enterica serovar Enteritidis (S. Enteritidis) is a commonly reported pathogen which adapts to multiple hosts and causes critical disease burden at a global level. Here, we investigated a recently derived epidemic sublineage with multidrug resistance (MDR), which have caused extended time-period and cross-regional gastroenteritis outbreaks and even invasive nontyphoidal Salmonella disease (iNTS) in China.

Whole-genome sequencing and antimicrobial resistance (AMR) testing were applied to 729 Chinese S. Enteritidis isolates in relation to gastroenteritis outbreaks, gastrointestinal-sporadic and iNTS infections, spanning 28 years (1994–2021) in China. Phylogenomic analysis was performed to explore the population structure and evolutionary history of the Chinese isolates within a global context. Molecular investigations of AMR genes, virulence factors, mobile genetic elements and pan-genomes were also performed.

The Chinese S. Enteritidis collections exhibited a high level of multidrug resistance (MDR), including high resistance to nalidixic acid (97.67%). Notably, the multidrug resistance rate of iNTS strains has significantly increased over the past decade. Phylogenomic analysis showed that the majority of the Chinese isolates (98.63%) were distributed in the global pandemic lineage L1, while the other lineages were highly continent-specific. Particularly, the Chinese isolates were predominantly distributed in sublineages L1.2 (37.45%) and L1.3 (59.26%), forming two main Chinese clades (MCC1&2). The most recent common ancestor of MCC1&2 dated back to 1944 and 2004, respectively. The lineage L1, especially MCC1&2, harbored the most amount of AMR determinants and virulence genes, which was mainly due to the presence of a hybrid virulence-resistance plasmid and coexistence of different types of AMR plasmids in S. Enteritidis.

S. Enteritidis has evolved unique clonal clusters, MCC1&2, with critical MDR in China, which phylogenetically constitute an extension of the globally epidemic lineage and were characterized by distinct genetic traits. These clades have induced extensive outbreaks of gastroenteritis and serious cases of iNTS in China, underscoring the pressing nature and severity of this public health crisis. Implementing the One-Health strategy, longstanding routine surveillance and further genomic epidemiological studies are urgently required to capture epidemics, monitor changes in bacterial populations and determine the consequent risk to global public health.