Metabolomics : Official journal of the Metabolomic Society最新文献

{"title":"Comprehensive profiling of semi-polar phytochemicals in whole wheat grains (Triticum aestivum) using liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry.","authors":"Leslie Tais,&nbsp;Hartwig Schulz,&nbsp;Christoph Böttcher","doi":"10.1007/s11306-020-01761-4","DOIUrl":"https://doi.org/10.1007/s11306-020-01761-4","url":null,"abstract":"<p><strong>Introduction: </strong>Wheat (Triticum aestivum) it is one of the most important staple food crops worldwide and represents an important resource for human nutrition. Besides starch, proteins and micronutrients wheat grains accumulate a highly diverse set of phytochemicals.</p><p><strong>Objectives: </strong>This work aimed at the development and validation of an analytical workflow for comprehensive profiling of semi-polar phytochemicals in whole wheat grains.</p><p><strong>Method: </strong>Reversed-phase ultra-high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-QTOFMS) was used as analytical platform. For annotation of metabolites accurate mass collision-induced dissociation mass spectra were acquired and interpreted in conjunction with literature data, database queries and analyses of reference compounds.</p><p><strong>Results: </strong>Based on reversed-phase UHPLC/ESI-QTOFMS an analytical workflow for comprehensive profiling of semi-polar phytochemicals in whole wheat grains was developed. For method development the extraction procedure and the chromatographic separation were optimized. Using whole grains of eight wheat cultivars a total of 248 metabolites were annotated and characterized by chromatographic and tandem mass spectral data. Annotated metabolites comprise hydroquinones, hydroxycinnamic acid amides, flavonoids, benzoxazinoids, lignans and other phenolics as well as numerous primary metabolites such as nucleosides, amino acids and derivatives, organic acids, saccharides and B vitamin derivatives. For method validation, recovery rates and matrix effects were determined for ten exogenous model compounds. Repeatability and linearity were assessed for 39 representative endogenous metabolites. In addition, the accuracy of relative quantification was evaluated for six exogenous model compounds.</p><p><strong>Conclusions: </strong>In conjunction with non-targeted and targeted data analysis strategies the developed analytical workflow was successfully applied to discern differences in the profiles of semi-polar phytochemicals accumulating in whole grains of eight wheat cultivars.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"18"},"PeriodicalIF":3.6,"publicationDate":"2021-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-020-01761-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38867155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GC-MS/MS analysis of metabolites derived from a single human blastocyst.","authors":"Naomi Inoue,&nbsp;Yoshihiro Nishida,&nbsp;Emi Harada,&nbsp;Kumiko Sakai,&nbsp;Hisashi Narahara","doi":"10.1007/s11306-021-01770-x","DOIUrl":"https://doi.org/10.1007/s11306-021-01770-x","url":null,"abstract":"<p><strong>Introduction: </strong>The field of assisted reproductive technology (ART) has significantly advanced; however, morphological evaluation remains as the chosen method of assessment of embryo quality.</p><p><strong>Objective: </strong>We aimed to examine metabolic changes in embryo culture medium to develop a non-invasive method for evaluation of embryo quality.</p><p><strong>Methods: </strong>We performed metabolic analysis of culture medium obtained from a single blastocyst cultured for freezing.</p><p><strong>Results: </strong>In total, 187 (39.8%) of the 469 detectable organic acid metabolites were identified. A significant change (p < 0.05) was observed in eight metabolites between the good-quality and poor-quality embryo groups. Differences were observed in several metabolic pathways between the good-quality and poor-quality embryo groups. Metabolites that showed significant changes were primarily involved in the metabolism of branched-chain amino acids.</p><p><strong>Conclusion: </strong>The quantification of metabolism in human embryos may assist in identification and selection of good-quality embryos with high rates of survival before freezing and implantation in conjunction with morphological classification. This may help to identify embryos with high rates of survival.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"17"},"PeriodicalIF":3.6,"publicationDate":"2021-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-021-01770-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38860063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic fingerprint of progression of chronic hepatitis B: changes in the metabolome and novel diagnostic possibilities.","authors":"Hien Thi Thu Nguyen,&nbsp;Reinhard Wimmer,&nbsp;Vang Quy Le,&nbsp;Henrik Bygum Krarup","doi":"10.1007/s11306-020-01767-y","DOIUrl":"https://doi.org/10.1007/s11306-020-01767-y","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic hepatitis B (CHB) affects 257 million individuals worldwide with an annual estimated mortality rate of 880,000 individuals. Accurate diagnosis of the stage of disease is difficult, and there is considerable uncertainty concerning the optimal point in time, when treatment should be started.</p><p><strong>Objectives: </strong>By analyzing and comparing the metabolomes of patients at different stages of CHB and comparing them to healthy individuals, we want to determine the metabolic signature of disease progression and develop a more accurate metabolome-based method for diagnosis of disease progression ultimately giving a better basis for treatment decisions.</p><p><strong>Methods: </strong>In this study, we used the combination of transient elastography and serum metabolomics of 307 serum samples from a group of 90 patients with CHB before and under treatment (with a follow-up time up to 10 years) at different progression stages over the clinical phases and 43 healthy controls..</p><p><strong>Results: </strong>Our data show that the metabolomics approach can successfully discover CHB changing from the immune tolerance to the immune clearance phase and show distinctive metabolomes from different medical treatment stages. Perturbations in ammonia detoxification, glutamine and glutamate metabolism, methionine metabolism, dysregulation of branched-chain amino acids, and the tricarboxylic acid (TCA) cycle are the main factors involved in the progression of the disease. Fluctuations increasing in aspartate, glutamate, glutamine, methionine and 13 other metabolites are fingerprints of progression.</p><p><strong>Conclusions: </strong>The metabolomics approach may expand the diagnostic armamentarium for patients with CHB. This method can provide a more detailed decision basis for starting medical treatment.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"16"},"PeriodicalIF":3.6,"publicationDate":"2021-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-020-01767-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38780957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.","authors":"Zackery W Reavis,&nbsp;Nikhil Mirjankar,&nbsp;Srikant Sarangi,&nbsp;Stephen H Boyle,&nbsp;Cynthia M Kuhn,&nbsp;Wayne R Matson,&nbsp;Michael A Babyak,&nbsp;Samantha A Matson,&nbsp;Ilene C Siegler,&nbsp;Rima Kaddurah-Daouk,&nbsp;Edward C Suarez,&nbsp;Redford B Williams,&nbsp;Katherine Grichnik,&nbsp;Mark Stafford-Smith,&nbsp;Anastasia Georgiades","doi":"10.1007/s11306-020-01757-0","DOIUrl":"https://doi.org/10.1007/s11306-020-01757-0","url":null,"abstract":"<p><strong>Introduction: </strong>Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown.</p><p><strong>Objective: </strong>Our objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men).</p><p><strong>Methods: </strong>CSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33 = .0015).</p><p><strong>Results: </strong>Multivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences.</p><p><strong>Conclusion: </strong>Several of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"13"},"PeriodicalIF":3.6,"publicationDate":"2021-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-020-01757-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38832762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic consequences for mice lacking Endosialin: LC-MS/MS-based metabolic phenotyping of serum from C56Bl/6J Control and CD248 knock-out mice.","authors":"Emily G Armitage, Alan Barnes, Kieran Patrick, Janak Bechar, Matthew J Harrison, Gareth G Lavery, G Ed Rainger, Christopher D Buckley, Neil J Loftus, Ian D Wilson, Amy J Naylor","doi":"10.1007/s11306-020-01764-1","DOIUrl":"10.1007/s11306-020-01764-1","url":null,"abstract":"<p><strong>Introduction: </strong>The Endosialin/CD248/TEM1 protein is expressed in adipose tissue and its expression increases with obesity. Recently, genetic deletion of CD248 has been shown to protect mice against atherosclerosis on a high fat diet.</p><p><strong>Objectives: </strong>We investigated the effect of high fat diet feeding on visceral fat pads and circulating lipid profiles in CD248 knockout mice compared to controls.</p><p><strong>Methods: </strong>From 10 weeks old, CD248^-/- and ^+/+ mice were fed either chow (normal) diet or a high fat diet for 13 weeks. After 13 weeks the metabolic profiles and relative quantities of circulating lipid species were assessed using ultra high performance liquid chromatography-quadrupole time-of flight mass spectrometry (UHPLC-MS) with high resolution accurate mass (HRAM) capability.</p><p><strong>Results: </strong>We demonstrate a specific reduction in the size of the perirenal fat pad in CD248^-/- mice compared to CD248^+/+, despite similar food intake. More strikingly, we identify significant, diet-dependent differences in the serum metabolic phenotypes of CD248 null compared to age and sex-matched wildtype control mice. Generalised protection from HFD-induced lipid accumulation was observed in CD248 null mice compared to wildtype, with particular reduction noted in the lysophosphatidylcholines, phosphatidylcholines, cholesterol and carnitine.</p><p><strong>Conclusions: </strong>Overall these results show a clear and protective metabolic consequence of CD248 deletion in mice, implicating CD248 in lipid metabolism or trafficking and opening new avenues for further investigation using anti-CD248 targeting agents.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2021-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38832913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted metabolomics as a diagnostic tool in NAFLD: discrimination of steatosis, steatohepatitis and cirrhosis.","authors":"Mario Masarone,&nbsp;Jacopo Troisi,&nbsp;Andrea Aglitti,&nbsp;Pietro Torre,&nbsp;Angelo Colucci,&nbsp;Marcello Dallio,&nbsp;Alessandro Federico,&nbsp;Clara Balsano,&nbsp;Marcello Persico","doi":"10.1007/s11306-020-01756-1","DOIUrl":"https://doi.org/10.1007/s11306-020-01756-1","url":null,"abstract":"<p><strong>Introduction: </strong>Non-Alcoholic Fatty Liver Disease encompasses a spectrum of diseases ranging from simple steatosis to steatohepatitis (or NASH), up to cirrhosis and hepatocellular carcinoma (HCC). The challenge is to recognize the more severe and/or progressive pathology. A reliable non-invasive method does not exist. Untargeted metabolomics is a novel method to discover biomarkers and give insights on diseases pathophysiology.</p><p><strong>Objectives: </strong>We applied metabolomics to understand if simple steatosis, steatohepatitis and cirrhosis in NAFLD patients have peculiar metabolites profiles that can differentiate them among each-others and from controls.</p><p><strong>Methods: </strong>Metabolomics signatures were obtained from 307 subjects from two separated enrollments. The first collected samples from 69 controls and 144 patients (78 steatosis, 23 NASH, 15 NASH-cirrhosis, 8 HCV-cirrhosis, 20 cryptogenic cirrhosis). The second, used as validation-set, enrolled 44 controls and 50 patients (34 steatosis, 10 NASH and 6 NASH-cirrhosis).The \"Partial-Least-Square Discriminant-Analysis\"(PLS-DA) was used to reveal class separation in metabolomics profiles between patients and controls and among each class of patients, and to reveal the metabolites contributing to class differentiation.</p><p><strong>Results: </strong>Several metabolites were selected as relevant, in particular:Glycocholic acid, Taurocholic acid, Phenylalanine, branched-chain amino-acids increased at the increase of the severity of the disease from steatosis to NASH, NASH-cirrhosis, while glutathione decreased (p < 0.001 for each). Moreover, an ensemble machine learning (EML) model was built (comprehending 10 different mathematical models) to verify diagnostic performance, showing an accuracy > 80% in NAFLD clinical stages prediction.</p><p><strong>Conclusions: </strong>Metabolomics profiles of NAFLD patients could be a useful tool to non-invasively diagnose NAFLD and discriminate among the various stages of the disease, giving insights into its pathophysiology.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"12"},"PeriodicalIF":3.6,"publicationDate":"2021-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-020-01756-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38764372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary metabolite levels in perinatally HIV-infected youth with periodontal disease.","authors":"Fabian Schulte,&nbsp;Oliver D King,&nbsp;Bruce J Paster,&nbsp;Anna-Barbara Moscicki,&nbsp;Tzy-Jyun Yao,&nbsp;Russell B Van Dyke,&nbsp;Caroline Shiboski,&nbsp;Mark Ryder,&nbsp;George Seage,&nbsp;Markus Hardt","doi":"10.1007/s11306-020-01719-6","DOIUrl":"https://doi.org/10.1007/s11306-020-01719-6","url":null,"abstract":"<p><strong>Introduction: </strong>Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels.</p><p><strong>Objective: </strong>As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU.</p><p><strong>Methods: </strong>We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them.</p><p><strong>Results: </strong>We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection.</p><p><strong>Conclusion: </strong>The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"98"},"PeriodicalIF":3.6,"publicationDate":"2020-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-020-01719-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38368021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MetaboShiny: interactive analysis and metabolite annotation of mass spectrometry-based metabolomics data.","authors":"Joanna C Wolthuis,&nbsp;Stefania Magnusdottir,&nbsp;Mia Pras-Raves,&nbsp;Maryam Moshiri,&nbsp;Judith J M Jans,&nbsp;Boudewijn Burgering,&nbsp;Saskia van Mil,&nbsp;Jeroen de Ridder","doi":"10.1007/s11306-020-01717-8","DOIUrl":"https://doi.org/10.1007/s11306-020-01717-8","url":null,"abstract":"<p><p>Direct infusion untargeted mass spectrometry-based metabolomics allows for rapid insight into a sample's metabolic activity. However, analysis is often complicated by the large array of detected m/z values and the difficulty to prioritize important m/z and simultaneously annotate their putative identities. To address this challenge, we developed MetaboShiny, a novel R/RShiny-based metabolomics package featuring data analysis, database- and formula-prediction-based annotation and visualization. To demonstrate this, we reproduce and further explore a MetaboLights metabolomics bioinformatics study on lung cancer patient urine samples. MetaboShiny enables rapid and rigorous analysis and interpretation of direct infusion untargeted mass spectrometry-based metabolomics data.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"99"},"PeriodicalIF":3.6,"publicationDate":"2020-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-020-01717-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38367587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrated omics approach to investigate summer mortality of New Zealand Greenshell™ mussels.","authors":"Siming Li,&nbsp;Andrea C Alfaro,&nbsp;Thao V Nguyen,&nbsp;Tim Young,&nbsp;Ronald Lulijwa","doi":"10.1007/s11306-020-01722-x","DOIUrl":"https://doi.org/10.1007/s11306-020-01722-x","url":null,"abstract":"<p><strong>Background: </strong>Green-lipped mussels, commercially known as Greenshell™ mussels (Perna canaliculus Gmelin 1791), contribute > $300 million to New Zealand's aquaculture exports. However, mortalities during summer months and potential pathogenic outbreaks threaten the industry. Thermal stress mechanisms and immunological responses to pathogen infections need to be understood to develop health assessment strategies and early warning systems.</p><p><strong>Methods: </strong>P. canaliculus were collected during a mortality event at a commercial aquaculture farm in Firth of Thames, New Zealand. Gill tissues from six healthy and six unhealthy mussels were excised and processed for metabolomic (GC-MS) and label-free proteomic (LC-MS) profiling. Univariate analyses were conducted separately on each data layer, with data being integrated via sparse multiple discriminative canonical correlation analysis. Pathway enrichment analysis was used to probe coordinated changes in functionally related metabolite sets.</p><p><strong>Results: </strong>Findings revealed disruptions of the tricarboxylic acid (TCA) cycle and fatty acid metabolism in unhealthy mussels. Metabolomics analyses also indicated oxidative stress in unhealthy mussels. Proteomics analyses identified under-expression of proteins associated with cytoskeleton structure and regulation of cilia/flagellum in gill tissues of unhealthy mussels. Integrated omics revealed a positive correlation between Annexin A4 and CCDC 150 and saturated fatty acids, as well as a negative correlation between 2-aminoadipic acid and multiple cytoskeletal proteins.</p><p><strong>Conclusions: </strong>Our study demonstrates the ability of using integrative omics to reveal metabolic perturbations and protein structural changes in the gill tissues of stressed P. canaliculus and provides new insight into metabolite and protein interactions associated with incidences of summer mortality in this species.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"100"},"PeriodicalIF":3.6,"publicationDate":"2020-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-020-01722-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38367925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycobacterium tuberculosis curli pili (MTP) deficiency is associated with alterations in cell wall biogenesis, fatty acid metabolism and amino acid synthesis.","authors":"S Ashokcoomar,&nbsp;K S Reedoy,&nbsp;S Senzani,&nbsp;D T Loots,&nbsp;D Beukes,&nbsp;M van Reenen,&nbsp;B Pillay,&nbsp;M Pillay","doi":"10.1007/s11306-020-01720-z","DOIUrl":"https://doi.org/10.1007/s11306-020-01720-z","url":null,"abstract":"<p><strong>Introduction: </strong>In an effort to find alternative therapeutic interventions to combat tuberculosis, a better understanding of the pathophysiology of Mycobacterium tuberculosis is required. The Mycobacterium tuberculosis curli pili (MTP) adhesin, present on the surface of this pathogen, has previously been shown using functional genomics and global transcriptomics, to play an important role in establishing infection, bacterial aggregation, and modulating host response in vitro and in vivo.</p><p><strong>Objective: </strong>This investigation aimed to determine the role of MTP in modulating the metabolism of M. tuberculosis, using mtp gene-knockout mutant and complemented strains.</p><p><strong>Methods: </strong>Untargeted two-dimensional gas chromatography time-of-flight mass spectrometry, and bioinformatic analyses, were used to identify significant differences in the metabolite profiles among the wild-type, ∆mtp mutant and mtp-complemented strains, and validated with results generated by real-time quantitative PCR.</p><p><strong>Results: </strong>A total of 28 metabolites were found to be significantly altered when comparing the ∆mtp mutant and the wild-type strains indicating a decreased utilisation of metabolites in cell wall biogenesis, a reduced efficiency in the breakdown of fatty acids, and decreased amino acid biosynthesis in the former strain. Comparison of the wild-type to mtp-complement, and ∆mtp to mtp-complemented strains revealed 10 and 16 metabolite differences, respectively. Real-time quantitative PCR results supported the metabolomics findings. Complementation of the ∆mtp mutant resulted in a partial restoration of MTP function.</p><p><strong>Conclusion: </strong>The lack of the MTP adhesin resulted in various bacterial cell wall alterations and related metabolic changes. This study highlights the importance of MTP as a virulence factor and further substantiates its potential use as a suitable biomarker for the development of diagnostic tools and intervention therapeutics against TB.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"97"},"PeriodicalIF":3.6,"publicationDate":"2020-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-020-01720-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38368724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}