Modulation of biofilm exopolysaccharides by the Streptococcus mutans vicX gene

The cariogenic pathogen Streptococcus mutans effectively utilizes dietary sucrose for the synthesis of exopolysaccharide, which act as a scaffold for its biofilm, thus contributing to its pathogenicity, environmental stress tolerance, and antimicrobial resistance. The two-component system VicRK of S. mutans regulates a group of virulence genes that are associated with biofilm matrix synthesis. Knockout of vicX affects biofilm formation, oxidative stress tolerance, and transformation of S. mutans. However, little is known regarding the vicX-modulated structural characteristics of the exopolysaccharides underlying the biofilm formation and the phenotypes of the vicX mutants. Here, we identified the role of vicX in the structural characteristics of the exopolysaccharide matrix and biofilm physiology. The vicX mutant (SmuvicX) biofilms seemingly exhibited desertification with architecturally impaired exopolysaccharide-enmeshed cell clusters, compared with the UA159 strain (S. mutans wild type strain). Concomitantly, SmuvicX showed a decrease in water-insoluble glucan (WIG) synthesis and in WIG/water-soluble glucan (WSG) ratio. Gel permeation chromatography (GPC) showed that the WIG isolated from the SmuvicX biofilms had a much lower molecular weight compared with the UA159 strain indicating differences in polysaccharide chain lengths. A monosaccharide composition analysis demonstrated the importance of the vicX gene in the glucose metabolism. We performed metabolite profiling via 1H nuclear magnetic resonance spectroscopy, which showed that several chemical shifts were absent in both WSG and WIG of SmuvicX biofilms compared with the UA159 strain. Thus, the modulation of structural characteristics of exopolysaccharide by vicX provides new insights into the interaction between the exopolysaccharide structure, gene functions, and cariogenicity. Our results suggest that vicX gene modulates the structural characteristics of exopolysaccharide associated with cariogenicity, which may be explored as a potential target that contributes to dental caries management. Furthermore, the methods used to purify the EPS of S. mutans biofilms and to analyze multiple aspects of its structure (gel permeation chromatography, gas chromatography-mass spectrometry, and 1H nuclear magnetic resonance spectroscopy) may be useful approaches to determine the roles of other virulence genes for dental caries prevention

Anterior cingulate cortex-related connectivity in first-episode schizophrenia: a spectral dynamic causal modeling study with functional magnetic resonance imaging

Understanding the neural basis of schizophrenia (SZ) is important for shedding light on the neurobiological mechanisms underlying this mental disorder. Structural and functional alterations in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, and medial prefrontal cortex (MPFC) have been implicated in the neurobiology of SZ. However, the effective connectivity among them in SZ remains unclear. The current study investigated how neuronal pathways involving these regions were affected in first-episode SZ using functional magnetic resonance imaging (fMRI). Forty-nine patients with a first-episode of psychosis and diagnosis of SZ—according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision—were studied. Fifty healthy controls (HCs) were included for comparison. All subjects underwent resting state fMRI. We used spectral dynamic causal modeling (DCM) to estimate directed connections among the bilateral ACC, DLPFC, hippocampus, and MPFC. We characterized the differences using Bayesian parameter averaging (BPA) in addition to classical inference (t-test). In addition to common effective connectivity in these two groups, HCs displayed widespread significant connections predominantly involved in ACC not detected in SZ patients, but SZ showed few connections. Based on BPA results, SZ patients exhibited anterior cingulate cortico-prefrontal-hippocampal hyperconnectivity, as well as ACC-related and hippocampal-dorsolateral prefrontal-medial prefrontal hypoconnectivity. In summary, sDCM revealed the pattern of effective connectivity involving ACC in patients with first-episode SZ. This study provides a potential link between SZ and dysfunction of ACC, creating an ideal situation to associate mechanisms behind SZ with aberrant connectivity among these cognition and emotion-related regions