High density genomic surveillance and risk profiling of clinical Listeria monocytogenes subtypes in Germany, 2018-2021

Foodborne infections represent a significant public health concern, particularly when outbreaks affect many individuals over prolonged time. Systematic collection of pathogen isolates from infected patients, whole genome sequencing and phylogenetic analyses allow recognition and termination of outbreaks after source identification and risk profiling of abundant lineages. We here present a multi-dimensional analysis of >1,800 genome sequences from clinical L. monocytogenes isolates collected in Germany between 2018-2021. These isolates covered 62% of all notified cases and belonged to 188 infection clusters. 42% of these clusters were active for >12 months, 60% generated cases cross-regionally, including 11 multinational clusters. 37% of the clusters were caused by sequence type (ST) ST6, ST8 and ST1 clones and for selected clusters, we provide further epidemiological and genetic information. Frequencies of materno-fetal and brain infections allowed risk profiling of the most abundant STs, differentiating ST1 as hyper- and ST8, ST14, ST29 as well as ST155 as hypovirulent from ST6 with average virulence potential. Hepatocyte infection experiments confirmed these virulence differences. Inactivating mutations were found in several virulence and house-keeping genes, particularly in hypovirulent STs. Our work supports prioritization of clusters for epidemiological investigations and reinforces the need to analyse the mechanisms underlying hyper- and hypovirulence.