Listeria monocytogenes in the Genomic Era: Persistence Mechanisms, Disinfectant Tolerance, Virulence Diversity, and Evolving Food Safety Challenges in Ready‐to‐Eat Food Systems

Listeria monocytogenes is a ubiquitous Gram‐positive bacterium and the causative agent of listeriosis, one of the most lethal foodborne diseases, with case fatality rates of 20%–30% in susceptible populations. It grows at refrigeration temperatures, tolerates salt and modified atmosphere packaging, and survives exposure to quaternary ammonium compound (QAC) disinfectants. These traits make it a persistent threat in ready‐to‐eat (RTE) food systems. Whole‐genome sequencing (WGS) and core genome multilocus sequence typing (cgMLST) now resolve the population structure of this pathogen at unprecedented resolution. This review synthesizes the genomic basis of virulence, persistence, and disinfectant tolerance. It covers virulence islands (LIPI‐1 to LIPI‐4), internalins, stress survival islands (SSI‐1/SSI‐2), and mobile genetic elements that carry QAC and biocide tolerance. Two genomic risk categories are examined. Hypervirulent clonal complexes are groups of closely related strains over‐represented in severe human disease relative to food. Persistent strains are genotypically indistinguishable isolates recovered repeatedly from one facility over months to years. We also assess biofilms, antimicrobial resistance, and the effect of tolerance on sanitation efficacy. The main contribution of this review is an integrated framework for genomic surveillance. We show how WGS can be embedded in environmental monitoring, HACCP, and ISO 22000 systems, and how it connects to the 2024 EU criteria revision, EU Regulation 2025/179, and the U.S. zero‐tolerance policy. A One Health workflow linking human, food, and environmental genomic data is proposed to support proactive listeriosis risk management.