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.

Bimetallic paddlewheel complexes derived from imides of (S)-t-leucine adopt ‘chiral crown’ configurations in which the four imide groups are projected in a chiral arrangement on one face, and the four t-butyl groups are projected on the opposite face. In this contribution, the generality of the chiral crown conformation is examined through crystallographic studies where the metal and the nature of the chiral ligands are altered. Based upon these observations, a model is proposed to explain the factors which create bias for the chiral crown configuration.

Background Bacterial vaginosis (BV) is a common imbalance of the vaginal microbiota characterized by overgrowth of diverse Actinobacteria, Firmicutes, and Gram-negative anaerobes. Women with BV are at increased risk of secondary reproductive tract infections and adverse pregnancy outcomes. However, which specific bacteria cause clinical features of BV is unclear. Methods We previously demonstrated that Gardnerella vaginalis could elicit many BV features in mice. In this study, we established a BV model in which we coinfected mice with G. vaginalis and another species commonly found in women with BV: Prevotella bivia. Results This coinfection model recapitulates several aspects of human BV, including vaginal sialidase activity (a diagnostic BV feature independently associated with adverse outcomes), epithelial exfoliation, and ascending infection. It is notable that G. vaginalis facilitated uterine infection by P. bivia. Conclusions Taken together, our model provides a framework for advancing our understanding of the role of individual or combinations of BV-associated bacteria in BV pathogenesis.

Sialic acids (neuraminic acids) are a diverse family of 9 carbon (nonulosonic) α-keto acidic carbohydrates. The canonical sialic acid, 2-keto-3-deoxy-5-acetamido-D-glycero-D-galactononulosonic acid, also known as N-acetylneuraminic acid (Neu5Ac) is the backbone on which a large number of known modifications are made (6). The Neu5Ac structure is typified by a 6 carbon carboxylic acid ring structure with a glycerol tail, an acetamido at the C-5 position and hydroxyl groups present on C-4, C-7, C-8, and C-9. Modifications occur primarily on the hydroxyl groups, with O-acetylation being the most common alteration, and substitutions have been shown to occur after the completion of the core structure (18). Other modifications such as O-methylation, O-lactylation, and O-sulfation add to the diversity of this molecule in vivo. Two structurally similar sialic acids, N-glycolylneuraminic acid (Neu5Gc), which differs from Neu5Ac by the presence of a hydroxyl group on the N-5 acetyl moiety, and 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid (KDN), a deaminated form of Neu5Ac also occur in nature and similar modifications are made to their core structure (6). These three main structures (Neu5Ac, Neu5Gc, and KDN) encompass the family of sialic acids due to their retention of the same stereochemical configuration of the 9-carbon backbone.