Project description:Bathymodiolus mussels inhabiting deep-sea hydrothermal vents harbor bacterial symbionts in their gills, which support the animals’ diet. While the basic mechanisms of energy generation and CO2 fixation that drive these symbioses are largely established, details of molecular interactions between the symbiotic partners and adaptations to their respective habitats remain unknown. In this study, we therefore comparatively examined the genomes and proteomes of two Bathymodiolus hosts and their respective symbionts from different geographical locations. Two mussel species were proteomically compared: i) B. thermophilus mussel containing sulfur-oxidizing symbiont from the east pacific rise. thermophilus and ii) B. azoricus containing thiotrophic and methanotrophic symbionts from the mid-atlantic ridge. Symbionts (for both species) and host components (for B. azoricus) were selectively enriched using a multi-step centrifugation procedure. Enriched host and symbiont fractions along with unenriched gill foot tissue were subject to in-depth semi-quantitative proteomic analyses using the orbitrap and velos mass spectrometers. Proteins were quantified based on their spectral counts using the normalized spectral abundance factor (NSAF) method. We identified common strategies of metabolic interactions that provide mutual nutritional support between host and symbionts, such as the detoxification of ambient sulfide by the Bathymodiolus host, which provides a stable thiosulfate reservoir for the thiotrophic symbionts, and a putative amino acid cycling mechanism that could supply the host with symbiont-derived amino acids. A suite of genes and proteins putatively related to virulence or defense functions was particularly abundant in the B. thermophilus symbiont, compared to its symbiont relatives, and may pose a host species-specific adaptation. Our results reveal both, a high degree of integration between the symbiotic partners, and great potential to adapt to the prevailing environment, which facilitate the holobiont’s survival in its hydrothermal vent habitat.

Project description:Bisphenols are used in the process of polymerization of polycarbonate plastics and epoxy resins, which have numerous applications in a variety of consumer products. Due to their hydrophobic properties, bisphenols can easily migrate out of plastic products especially into fatty foods. They have been found in brain, liver, adipose tissue and body fluids, illustrating their environmental prevalence. By increasing colonic inflammation in mice, disrupting the intestinal bacterial community structure and altering the microbial membrane transport system in zebrafish, bisphenols seem to interfere with the gut microbiome. The highly abundant human commensal bacterium Bacteroides thetaiotaomicron was exposed to bisphenols (Bisphenol A (BPA), Bisphenol F (BPF), Bisphenol S (BPS)), to examine the mode of action, in particular of BPF. All chemicals caused a concentration-dependent growth inhibition and the half-maximal effective concentration (EC50) corresponded to their individual logP values, a measure of their hydrophobicity. B. thetaiotaomicron exposed to BPF decreased membrane fluidity with increasing BPF concentrations. Physiological changes including an increase of acetate concentration were observed in cells treated with 0.57 mM BPF. On the proteome level, a higher abundance of several ATP synthase subunits and multidrug efflux pumps suggested an increased energy demand for adaptive mechanisms after BPF exposure. Defence mechanisms were also implicated by a pathway analysis, that identified a higher abundance of members of resistance pathways/strategies to cope with xenobiotics (i.e. antibiotics). Here, we present further insights into the mode of action of bisphenols in a human commensal gut bacterium regarding growth inhibition, and the physiological and functional state of the cell. These results, combined with microbiota-directed effects, could lead to a better understanding of host health disturbances and disease development based on xenobiotic uptake.

Project description:The relationship between repetitive mild traumatic brain injury (r-mTBI) and Alzheimer’s disease (AD) is well-recognized. However, the precise nature of how r-mTBI leads to or precipitates AD pathogenesis is currently not understood. Part A: Plasma biomarkers potentially provide non-invasive tools for detecting neurological changes in the brain, and can reveal overlaps between long-term consequences of r-mTBI and AD. In this study we address this by generating time-dependent molecular profiles of response to r-mTBI and AD pathogenesis in mouse models using unbiased proteomic analyses. To model AD, we used the well-validated hTau and PSAPP(APP/PS1) mouse models that develop age-related tau and amyloid pathological features respectively, and our well-established model of r-mTBI in C57BL/6 mice. Plasma were collected at different ages (3, 9, and 15 months-old for hTau and PSAPP mice), encompassing pre-, peri- and post-“onset” of the cognitive and neuropathological phenotypes, or at different timepoints after r-mTBI (24hrs, 3, 6, 9 and 12 months post-injury). Liquid chromatography/mass spectrometry (LC-MS) approaches coupled with Tandem Mass Tag labeling technology were applied to develop molecular profiles of protein species that were significantly differentially expressed as a consequence of mTBI or AD. Mixed model ANOVA after Benjamini-Hochberg correction, and a stringent cut-off identified 31 proteins significantly changing in r-mTBI groups over time and, when compared with changes over time in sham mice, 13 of these were unique to the injured mice. The canonical pathways predicted to be modulated by these changes were LXR/RXR activation, production of nitric oxide and reactive oxygen species and complement systems. We identified 18 proteins significantly changing in PSAPP mice and 19 proteins in hTau mice compared to their wildtype littermates with ageing. Six proteins were found to be significantly regulated in all three models i.e. r-mTBI, hTau and PSAPP mice compared to their controls. The top canonical pathways coincidently changing in all three models were LXR/RXR activation, and production of nitric oxide and reactive oxygen species. This work suggests potential biomarkers for TBI and AD pathogenesis and for the overlap between these two, and warrant targeted investigation in human populations. Part B: In this part of the study we address the above problem by utilizing our unbiased proteomic approach to generate detailed time-dependent brain molecular profiles of response to repetitive mTBI and AD pathogenesis in established mouse models. The same animal models described above were used herein. A LC/MS approach coupled with TMT labeling was also employed. Results: Mixed model ANOVA after Benjamin Hochberg correction identified 30 and 47 proteins that were specifically unique and changing in the hippocampus and cortex, respectively, within the r-mTBI group alone when compared with changes overtime in sham mice. PI3K/AKT signaling, Protein Kinase A signaling and PPAR/RXR activation in the hippocampus, and Protein Kinase A signaling, GNRH signaling and B cell receptor signaling in the cortex were the top canonical systems significantly altered in injury groups compared to sham mice. Mixed model AONVA identified 19 proteins significantly changing in the cortex of PSAPP mice and 7 proteins in hTau mice compared to their relative wildtype littermates respectively. In addition to the heterogeneous changes observed in the TBI and AD mouse models, there was a notable convergence and coincidental change in 6 unique proteins identified in the repetitive mTBI model and the hTau and PSAPP model. These proteins ostensibly indicate significant common pathobiological responses involving alterations in mitochondrial bioenergetics and energy metabolism, aberrant cytoskeletal reorganization and alterations in intracellular signaling transduction cascades. Conclusion: We believe that this work could help identify the common molecular substrates responsible for the precipitation of AD pathogenesis following repetitive mTBI, and also help to identify novel biological targets for therapeutic modulation in mTBI and AD.

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Bacillus licheniformis exponential phase

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