Host-Derived Sialic Acids Are an Important Nutrient Source Required for Optimal Bacterial Fitness In Vivo

Abstract

A major challenge facing bacterial intestinal pathogens is competition for nutrient sources with the host microbiota. Vibrio cholerae is an intestinal pathogen that causes cholera, which affects millions each year; however, our knowledge of its nutritional requirements in the intestinal milieu is limited. In this study, we demonstrated that V. cholerae can grow efficiently on intestinal mucus and its component sialic acids and that a tripartite ATP-independent periplasmic SiaPQM strain, transporter-deficient mutant NC1777, was attenuated for colonization using a streptomycin-pretreated adult mouse model. In in vivo competition assays, NC1777 was significantly outcompeted for up to 3 days postinfection. NC1777 was also significantly outcompeted in in vitro competition assays in M9 minimal medium supplemented with intestinal mucus, indicating that sialic acid uptake is essential for fitness. Phylogenetic analyses demonstrated that the ability to utilize sialic acid was distributed among 452 bacterial species from eight phyla. The majority of species belonged to four phyla, Actinobacteria (members of Actinobacillus, Corynebacterium, Mycoplasma, and Streptomyces), Bacteroidetes (mainly Bacteroides, Capnocytophaga, and Prevotella), Firmicutes (members of Streptococcus, Staphylococcus, Clostridium, and Lactobacillus), and Proteobacteria (including Escherichia, Shigella, Salmonella, Citrobacter, Haemophilus, Klebsiella, Pasteurella, Photobacterium, Vibrio, and Yersinia species), mostly commensals and/or pathogens. Overall, our data demonstrate that the ability to take up host-derived sugars and sialic acid specifically allows V. cholerae a competitive advantage in intestinal colonization and that this is a trait that is sporadic in its occurrence and phylogenetic distribution and ancestral in some genera but horizontally acquired in others.

Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut

“…Free sialic acid is a nutrient source for the antibiotic-associated enteric pathogens Clostridium difficile and Salmonella typhimurium , and can determine pathogen burden in mouse models (McDonald et al, 2016; Ng et al, 2013). Mucosal glycoproteins carrying sialic acid also serve as viral receptors (Wasik et al, 2016).…”

Glycan recognition at the saliva – oral microbiome interface

“…The ability to scavenge host sialic acids has also been observed in Haemophilus influenzae , Tannerella forsythia, and Vibrio cholerae . These species carry an orthologous N -acetylneuraminic acid lyase ( nanA ) gene, which is necessary in the first step of sialic acid catabolism [198, 204, 205]. The nanA gene has been found in other bacterial genera including Streptomyces , Streptococcus , Staphylococcus , Clostridium , Lactobacillus , Escherichia , Salmonella , and many more, suggesting that they may also be able to scavenge host sialic acids from their environment [204].…”

Vibrio vulnificus: From Oyster Colonist to Human Pathogen

“…This is an important aspect of pathogenicity to be investigated further, especially in pathogens capable of gastrointestinal infection, including V . vulnificus [16]. On the same theme, sialic acid-like carbohydrates factor into the pathogenicity of V .…”