A comprehensive review of regulatory mechanisms of novel enterotoxin genes in Staphylococcus aureus from meat sources

Background and aims Meat-borne Staphylococcus aureus (S. aureus) remains a leading global foodborne pathogen harbouring novel enterotoxin genes (NEGs) encoding superantigenic toxins with conditionally enhanced pathogenicity, representing a critical food safety hazard. This review characterizes NEG features, pathogenic mechanisms, multi-layered regulatory networks, and identifies key research challenges.Methods We systematically searched PubMed, Embase and the Web of Science Core Collection to synthesize molecular and multi-omics evidence (ChIP-seq, RNA-seq, CRISPR-Cas9) characterizing NEG classification, pathogenic mechanisms, multi-level regulatory networks (transcriptional, post-translational, environmental), and geographical distribution patterns in meat-derived S. aureus.Results NEGs comprise superantigenic and tissue-targeting subgroups mediating pathogenicity via cytotoxicity, intestinal microenvironment disruption, and immune evasion. Regulation involves a complex network of Agr/σB/SarA/Rot-mediated transcriptional control, phosphorylation/lactylation modifications and environmental sensing, exhibiting marked geographical divergence. Current limitations include technical resolution constraints, insufficient physiological model fidelity and incomplete regulatory crosstalk elucidation.Conclusions Future research should prioritize transcription factor interaction mechanisms, growth-toxin correlation prediction models and multi-omics-based network decipherment. This review provides a foundational framework for NEG research to inform food safety risk assessment and targeted contamination control strategies.