Nevertheless, they persist: addressing the stalemate of persistence in food-associated Listeria monocytogenes research.

Foodborne illness is a critical food safety and public health concern, often resulting from contamination events by resident pathogens in food processing environments (FPEs). Listeria monocytogenes, the causative agent of listeriosis, can persist in FPEs over long time periods. Despite rigorous research on the phenotypic and genotypic traits of L. monocytogenes, no clear pattern has arisen to explain why some strains are able to persist. Researchers face definitional and methodological challenges, which influence identification and comparison of persistent and non-persistent strains. Moreover, only weak associations between persistence and gene-level patterns have been detected, necessitating new perspectives. In this review, we synthesize years of research based on whole genome sequencing, highlighting sequence-type and gene-level patterns linked to persistence. As these patterns do not robustly explain persistence, we critically assess how applied definitions and methodological approaches have shaped, and potentially biased, our current understanding. We evaluate existing hypotheses on persistence and suggest future research directions, integrating insights from ecology, evolution, and predictive modeling to disentangle factors and mechanisms that enable L. monocytogenes to persist in food processing environments.