Sialic acid‐like molecules in motility, biofilm formation, and systemic pathogenesis by the seafood‐borne pathogen Vibrio vulnificus (LB144)

Abstract

Sialic acids are found on all vertebrate cell surfaces. Dozens of pathogens have evolved a variety of ways to mask themselves with sialic acids, which can promote bloodstream survival of pathogens via multiple mechanisms. Many other bacterial pathogens synthesize sialic acid‐like molecules to decorate lipopolysaccharides or flagella; however, the role(s) of sialic acid‐like molecules in the bloodstream have not been investigated. Vibrio vulnificus is a seafood‐borne pathogen and a leading cause of food‐related death in the U.S. because of its ability to quickly access the host bloodstream. However, virtually nothing is known about how this organism persists in the systemic vasculature. We previously showed that many clinical isolates of Vibrio vulnificus express high levels of sialic acid‐like molecules (di‐N‐acetylated nonulosonic acids or NulOs). Here we elucidate the genetic basis of NulO biosynthesis in V. vulnificus and, using an isogenic in‐frame deletion of the putative NulO synthase gene nab2, we demonstrate a vital role for these molecules in systemic virulence of V. vulnificus. The data show that V. vulnificus LPS are adorned with NulO residues and that expression of these molecules is required for optimal biofilm formation, motility and flagellar expression. Competition experiments in a mouse model of septecemia revealed a striking 500‐fold survival advantage of the WT versus nab2 strain. In summary, these data demonstrate several biological functions of sialic acid‐like molecules in V. vulnificus and provide the first molecular explanation for how members of this species cause life‐threatening systemic infections.