Exocytosis and protein secretion in Trypanosoma

<p>Abstract</p> <p>Background</p> <p>Human African trypanosomiasis is a lethal disease caused by the extracellular parasite <it>Trypanosoma brucei</it>. The proteins secreted by <it>T. brucei </it>inhibit the maturation of dendritic cells and their ability to induce lymphocytic allogenic responses. To better understand the pathogenic process, we combined different approaches to characterize these secreted proteins.</p> <p>Results</p> <p>Overall, 444 proteins were identified using mass spectrometry, the largest parasite secretome described to date. Functional analysis of these proteins revealed a strong bias toward folding and degradation processes and to a lesser extent toward nucleotide metabolism. These features were shared by different strains of <it>T. brucei</it>, but distinguished the secretome from published <it>T. brucei </it>whole proteome or glycosome. In addition, several proteins had not been previously described in <it>Trypanosoma </it>and some constitute novel potential therapeutic targets or diagnostic markers. Interestingly, a high proportion of these secreted proteins are known to have alternative roles once secreted. Furthermore, bioinformatic analysis showed that a significant proportion of proteins in the secretome lack transit peptide and are probably not secreted through the classical sorting pathway. Membrane vesicles from secretion buffer and infested rat serum were purified on sucrose gradient and electron microscopy pictures have shown 50- to 100-nm vesicles budding from the coated plasma membrane. Mass spectrometry confirmed the presence of <it>Trypanosoma </it>proteins in these microvesicles, showing that an active exocytosis might occur beyond the flagellar pocket.</p> <p>Conclusions</p> <p>This study brings out several unexpected features of the secreted proteins and opens novel perspectives concerning the survival strategy of <it>Trypanosoma </it>as well as possible ways to control the disease. In addition, concordant lines of evidence support the original hypothesis of the involvement of microvesicle-like bodies in the survival strategy allowing <it>Trypanosoma </it>to exchange proteins at least between parasites and/or to manipulate the host immune system.</p

Diet-Related Metabolites Associated with Cognitive Decline Revealed by Untargeted Metabolomics in a Prospective Cohort

Scope: Untargeted metabolomics may reveal preventive targets in cognitive aging, including within the food metabolome. Methods and results: A case-control study nested in the prospective Three-City study includes participants aged &65 years and initially free of dementia. A total of 209 cases of cognitive decline and 209 controls (matched for age, gen- der, education) with slower cognitive decline over up to 12 years are contrasted. Using untargeted metabolomics and bootstrap-enhanced penalized regression, a baseline serum signature of 22 metabolites associated with subsequent cognitive decline is identified. The signature includes three coffee metabolites, a biomarker of citrus intake, a cocoa metabolite, two metabolites putatively derived from fish and wine, three medium-chain acylcarnitines, glycodeoxycholic acid, lysoPC(18:3), trimethyllysine, glucose, cortisol, creatinine, and arginine. Adding the 22 metabolites to a reference predictive model for cognitive decline (conditioned on age, gender, education and including ApoE-ε4, diabetes, BMI, and number of medications) substantially increases the predictive performance: cross-validated Area Under the Receiver Operating Curve = 75% [95% CI 70-80%] compared to 62% [95% CI 56-67%]. Conclusions: The untargeted metabolomics study supports a protective role of specific foods (e.g., coffee, cocoa, fish) and various alterations in the endogenous metabolism responsive to diet in cognitive aging

Identification of Pre-frailty Sub-Phenotypes in Elderly Using Metabolomics

Aging is a dynamic process depending on intrinsic and extrinsic factors and its evolution is a continuum of transitions, involving multifaceted processes at multiple levels. It is recognized that frailty and sarcopenia are shared by the major age-related diseases thus contributing to elderly morbidity and mortality. Pre-frailty is still not well understood but it has been associated with global imbalance in several physiological systems, including inflammation, and in nutrition. Due to the complex phenotypes and underlying pathophysiology, the need for robust and multidimensional biomarkers is essential to move toward more personalized care. The objective of the present study was to better characterize the complexity of pre-frailty phenotype using untargeted metabolomics, in order to identify specific biomarkers, and study their stability over time. The approach was based on the NU-AGE project (clinicaltrials.gov, NCT01754012) that regrouped 1,250 free-living elderly people (65–79 y.o., men and women), free of major diseases, recruited within five European centers. Half of the volunteers were randomly assigned to an intervention group (1-year Mediterranean type diet). Presence of frailty was assessed by the criteria proposed by Fried et al. (2001). In this study, a sub-cohort consisting in 212 subjects (pre-frail and non-frail) from the Italian and Polish centers were selected for untargeted serum metabolomics at T0 (baseline) and T1 (follow-up). Univariate statistical analyses were performed to identify discriminant metabolites regarding pre-frailty status. Predictive models were then built using linear logistic regression and ROC curve analyses were used to evaluate multivariate models. Metabolomics enabled to discriminate sub-phenotypes of pre-frailty both at the gender level and depending on the pre-frailty progression and reversibility. The best resulting models included four different metabolites for each gender. They showed very good prediction capacity with AUCs of 0.93 (95% CI = 0.87–1) and 0.94 (95% CI = 0.87–1) for men and women, respectively. Additionally, early and/or predictive markers of pre-frailty were identified for both genders and the gender specific models showed also good performance (three metabolites; AUC = 0.82; 95% CI = 0.72–0.93) for men and very good for women (three metabolites; AUC = 0.92; 95% CI = 0.86–0.99). These results open the door, through multivariate strategies, to a possibility of monitoring the disease progression over time at a very early stage

Peptide Mass Fingerprinting: Identification of Proteins by MALDI-TOF

Peptide Mass Fingerprinting: Identification of Proteins by MALDI-TO

Label-free study of peptides released during in vitro digestion of bovine cooked meat

National audienc

Détermination de marqueurs précoces de stéatose par imagerie moléculaire du foie

National audienc

Development of a MALDI imaging mass spectrometry (IMS) approach to bacterial proteomics: first application to Listeria monocytogenes biofilms exposed to a desiccation

Development of a MALDI imaging mass spectrometry (IMS) approach to bacterial proteomics: first application to Listeria monocytogenes biofilms exposed to a desiccation. 7. Congress of European Microbiologists FEMS 201

MALDI imaging and profiling mass spectrometry approach for the analysis of Listeria monocytogenes biofilms exposed to a desiccation

MALDI imaging and profiling mass spectrometry approach for the analysis of Listeria monocytogenes biofilms exposed to a desiccation. SMMAP 2017, Spectrométrie de Masse, Métabolomique et Analyse Protéomiqu

Development of a Mass Spectrometry Imaging (MSI) approach to explore Listeria monocytogenes biofilms exposed to a dehumidification stress

Development of a Mass Spectrometry Imaging (MSI) approach to explore Listeria monocytogenes biofilms exposed to a dehumidification stress. 8. Colloque du Réseau National Biofilm

Le traitement par cures au paracétamol induit une réduction de la masse et la synthèse des protéines musculaires chez le rat âgé

This abstract has also been published in Cahiers de nutrition et de diététique 48 (2013) S23-S55absen