# Emergence, climate-driven expansion, and diversification of a European Vibrio vulnificus lineage (L4) with multi-host pathogenic potential

## TL;DR

A European Vibrio vulnificus lineage (L4) is expanding northward due to climate change and shows increased pathogenic potential across multiple hosts.

## Contribution

Discovery of a novel MARTX toxin variant and evidence of L4's northward expansion and multi-host pathogenicity in a warming climate.

## Key findings

- L4 isolates exhibit extensive genetic plasticity, including three MARTX toxin architectures and multiple prophages.
- A novel calmodulin-dependent NADase domain was identified in a previously undescribed MARTX variant (type H).
- L4 strains can resist iron-overloaded human serum, indicating sepsis-causing potential in humans.

## Abstract

Climate-driven changes are reshaping the ecology of Vibrio vulnificus in European waters. Here, we present a retrospective genomic and phenotypic analysis of pre-2018 isolates belonging to lineage 4 (L4), a phylogenetic group historically confined to the Mediterranean Sea and now detected in northern Europe. Using a lineage-specific multiplex PCR combined with whole-genome sequencing, we identified 49 clinical and environmental L4 isolates from German coastal waters. Comparative genomics revealed extensive genetic plasticity in L4, indicative of frequent recombination and horizontal gene transfer, including three MARTX toxin architectures, fourteen distinct capsular genotypes, two type VI secretion systems, and multiple prophages. Notably, nearly half of the L4 isolates encoded a previously undescribed MARTX variant (type H), apparently derived from recombination within a type C toxin and containing a novel calmodulin-dependent NADase (CdN) domain with potential functional implications for virulence. One strain also harboured the plasmid-borne genes ftbp and fpcrp, which confer resistance to fish innate immunity and the ability to cause sepsis, thereby extending the distribution of the piscis pathovar to all five V. vulnificus lineages. Functional assays showed that most L4 strains withstood the bactericidal activity of iron-overloaded human serum, consistent with a capacity to cause sepsis in susceptible individuals. Collectively, these findings redefine V. vulnificus as a multi-host climate-responsive marine pathogen and establish L4 as a newly adapted European lineage whose northward expansion exemplifies how genomic diversification and ocean warming jointly drive the evolution of high-risk marine pathogens within a One Health framework.