High density genomic surveillance and risk profiling of clinical Listeria monocytogenes subtypes in Germany

Abstract

Abstract Background Foodborne infections such as listeriosis caused by the bacterium Listeria monocytogenes 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 (WGS) and phylogenetic analyses allow recognition and termination of outbreaks after source identification and risk profiling of abundant lineages. Methods We here present a multi-dimensional analysis of > 1800 genome sequences from clinical L. monocytogenes isolates collected in Germany between 2018 and 2021. Different WGS-based subtyping methods were used to determine the population structure with its main phylogenetic sublineages as well as for identification of disease clusters. Clinical frequencies of materno-foetal and brain infections and in vitro infection experiments were used for risk profiling of the most abundant sublineages. These sublineages and large disease clusters were further characterised in terms of their genetic and epidemiological properties. Results The collected isolates covered 62% of all notified cases and belonged to 188 infection clusters. Forty-two percent of these clusters were active for > 12 months, 60% generated cases cross-regionally, including 11 multinational clusters. Thirty-seven percent of the clusters were caused by sequence type (ST) ST6, ST8 and ST1 clones. ST1 was identified as hyper- and ST8, ST14, ST29 as well as ST155 as hypovirulent, while ST6 had average virulence potential. Inactivating mutations were found in several virulence and house-keeping genes, particularly in hypovirulent STs. Conclusions Our work presents an in-depth analysis of the genomic characteristics of L. monocytogenes isolates that cause disease in Germany. It supports prioritisation of disease clusters for epidemiological investigations and reinforces the need to analyse the mechanisms underlying hyper- and hypovirulence.

Keywords

• Epidemiology
• Outbreak
• inlF
• flaR
• clpP1