Host-Like Carbohydrates Promote Bloodstream Survival of Vibrio vulnificusIn Vivo

Abstract

Sialic acids are found on all vertebrate cell surfaces and are part of a larger class of molecules known as nonulosonic acids. Many bacterial pathogens synthesize related nine-carbon backbone sugars; however, the role(s) of these non-sialic acid molecules in host-pathogen interactions is poorly understood. Vibrio vulnificus is the leading cause of seafood-related death in the United States due to its ability to quickly access the host bloodstream, which it can accomplish through gastrointestinal or wound infection. However, little is known about how this organism persists systemically. Here we demonstrate that sialic acid-like molecules are present on the lipopolysaccharide of V. vulnificus, are required for full motility and biofilm formation, and also contribute to the organism's natural resistance to polymyxin B. Further experiments in a murine model of intravenous V. vulnificus infection demonstrated that expression of nonulosonic acids had a striking benefit for bacterial survival during bloodstream infection and dissemination to other tissues in vivo. In fact, levels of bacterial persistence in the blood corresponded to the overall levels of these molecules expressed by V. vulnificus isolates. Taken together, these results suggest that molecules similar to sialic acids evolved to facilitate the aquatic lifestyle of V. vulnificus but that their emergence also resulted in a gain of function with life-threatening potential in the human host.

Discovery and characterization ofde novosialic acid biosynthesis in the phylumFusobacterium

“…The same is true among several other taxa that are known to produce sialic acids or related molecules Lubin et al 2015).…”

Vibrio vulnificus: From Oyster Colonist to Human Pathogen

“…vulnificus also variably produces sialic acid-like molecules presented as modifications to the lipopolysaccharide, which likely evolved to facilitate a marine environmental lifestyle. However, these modifications show significant benefit to survival during bloodstream infections and dissemination in vivo [15]. In addition, sialic acid is linked to metabolic fitness in the gut.…”

“…On the same theme, sialic acid-like carbohydrates factor into the pathogenicity of V . vulnificus , since these host-like molecules are required for full motility and biofilm formation, providing a benefit for bacterial survival in the bloodstream [15]. …”

Structural and functional characterization of CMP-N-acetylneuraminate synthetase fromVibrio cholerae

“…In a mouse model of septicaemia, competition experiments revealed that the V. vulnificus sialic acid synthase mutant strain has a 300-fold lower chance of survival compared with the wild-type strain. Sialic acid plays a critical role in biofilm formation and motility, and also protects V. vulnificus from the host immune response (Lubin et al, 2015). These data imply a critical role of the enzymes responsible for sialic acid utilization in the survival of V. vulnificus.…”