Whole-genome sequence-based surveillance of human clinical Listeria monocytogenes isolates from Switzerland, 2019–2024

Background Listeria monocytogenes is a foodborne pathogen that poses a significant public health risk due to the high case-fatality rate of listeriosis. Whole-genome sequencing (WGS) is critical for identifying outbreak clusters and enables high-resolution characterization of isolates. Methods We collected 335 L. monocytogenes isolates from human cases of listeriosis occurring in Switzerland between 2019 and 2024. WGS was used to identify disease clusters and characterize the phylogenetic relatedness, virulence profiles and antimicrobial resistance genes of the isolates. Findings The majority (77%) of the cases involved patients ≥ 65 years and was associated with bacteremia. The five major clonal complexes (CCs) were CC1, CC4, CC6, CC8, and CC388. The isolates belonged to 35 infection clusters, including three large outbreak clusters of 21 -37 isolates per cluster. Nine smaller clusters included isolates highly related to food isolates obtained up to four years earlier. Multiple singly occurring isolates were linked to international outbreaks. WGS identified variations within key virulence factors including premature stop codons in InlA, length polymorphisms of ActA, and amino acid substitutions within PrfA. Hypervirulence associated with Listeria pathogenicity island (LIPI)-3 was found predominantly among CC1, CC4, and CC6 isolates. LIPI-4 was present in CC4 and CC388, and in infrequently occurring ST32, ST213, ST217, ST220, ST382, and ST1460. Interpretation High-resolution typing of L. monocytogenes is effective for the detection of disease clusters and for linking cases to international outbreaks. The identification of rare hypervirulent lineages demonstrates the importance of investigating the phylogenetic relatedness and virulence profiles of clinical L. monocytogenes.