Rising <i>Vibrio vulnificus</i> Infections in Northern Europe Linked to Environmental Reservoirs Sustaining Clinical Pathogenicity

Abstract

Vibrio vulnificus is one of the most lethal marine pathogens, causing wound infections, septicemia, and necrotizing soft tissue infection with case fatality rates exceeding 20-50%. In Northern Europe, incidence is rising alongside warming coastal waters. The genomic relatedness between environmental and clinical isolates and the long-term persistence of virulent clades in temperate waters remains poorly defined. An analysis of 117 V. vulnificus genomes, including 60 newly sequenced (36 environmental isolates and 24 clinical isolates from Denmark 1994-2023), 27 publicly available Nordic clinical genomes, and 30 comparative reference public genomes were analyzed. Comparative genomics, virulence gene profiling, pangenome analysis, and core-genome SNP phylogeny were used to define clade structure, persistence, and genetic determinants of pathogenicity. Four major clades were identified; three (C2-C4) persisted for up to three decades and contained both clinical and environmental isolates. Clonal pairs (≤40 SNPs) linked environmental and clinical sources across up to eight years and multiple countries. The virulence gene repertoire including the major virulence factors MARTX toxin genes (rtxA/B/C/D), chiRP (chitin-regulated pilus), flp2/tad2 pili (fimbrial low-molecular-weight protein/tight adherence pili), ilpA (immunogenic lipoprotein A), ompU (outer membrane porin), and vvhA (V. vulnificus hemolysin).) were present in both environmental and clinical isolates. All isolates carried the tetracycline resistance gene tet(34). We report that environmental aquatic reservoirs harbor fully virulent V. vulnificus lineages, making human infections exposure-driven rather than the result of emerging novel lineages.