MetaboLights

application/xml

ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/m_MTBLS11617_LC-MS_positive_hilic_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/m_MTBLS11617_LC-MS_negative_hilic_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/a_MTBLS11617_LC-MS_positive_hilic_metabolite_profiling.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/s_MTBLS11617.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/a_MTBLS11617_LC-MS_negative_hilic_metabolite_profiling.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/FRAG_NEG.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/FRAG_POS.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/FRAG_NEG.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank6.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std2_1_02AUG18.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_9.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std1_1_02AUG18.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_8.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/FRAG_POS.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_7.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_10.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/cmw.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std3_1_02AUG18.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank3_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank1.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B4.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B1.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_7_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank4.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_8.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std2_1_02AUG18.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A2.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C3.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_10.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B2_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std3_1_02AUG18_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std1_1_02AUG18.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank4_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A3.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B3.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B2.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A3_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank5.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C2.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C2_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_7.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_10_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B1_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/cmw.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A4_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A1.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C4.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A4.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_9_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank6.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C3_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C1.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank1_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std2_1_02AUG18_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std3_1_02AUG18.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank5_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B4_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A1_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank2.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_8_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C4_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/C1_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/pooled_9.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank2_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/A2_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank3.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/Std1_1_02AUG18_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/B3_neg.mzXMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617/FILES/matrix_blank6_neg.mzXMLprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS11617Identification of metabolites was based on fragmentation spectra, retention time and mass compared to authentic standards as previously outlined by the metabolomics standards initiative (MSI)[1]. Metabolites that matched an authentic standard with or without a fragmentation spectrum were classified as identified (MSI level 1). Metabolites which did not match to any authentic standards but had spectral similarities with spectral libraries https://www.genome.jp/kegg/pathway.html, were classified as putatively annotated and analysed further based on fragmentation spectra if available. Ref:[1] Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA, Fan TW, Fiehn O, Goodacre R, Griffin JL, Hankemeier T, Hardy N, Harnly J, Higashi R, Kopka J, Lane AN, Lindon JC, Marriott P, Nicholls AW, Reily MD, Thaden JJ, Viant MR. Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics. 2007 Sep;3(3):211-221. doi:10.1007/s11306-007-0082-2. PMID:24039616.MetaboLightsPublicLiquid Chromatography MS - positive - hilicLiquid Chromatography MS - negative - hilicMetabolomics samples were separated using a high-performance liquid chromatography (HPLC) system (Dionex) with a ZIC-pHILIC column (Merck SeQuant) as before (A. W. Pountain, M. P. Barrett, Untargeted metabolomics to understand the basis of phenotypic differences in amphotericin B-resistant Leishmania parasites. Wellcome Open Research 4, 176 (2019).)Anopheles mosquito survival and pharmacokinetic modeling show the mosquitocidal activity of nitisinone. 10.1126/scitranslmed.adr4827. PMID:40138457Clement RegnaultUniversity of Glasgowmixturesample preparation blankWhole Organismmass spectrometry assayFrozen samples were shipped to the Glasgow Polyomics Facility on dry ice and processed in house according to well established protocols. Briefly, samples were ground on dry ice using handheld homogeniser (VWR, Cordless Motor - Pestle Motor, Model 47747-370). Homogenate was re-suspended in 200 µl of extraction solvent (chloroform/methanol/water, 1:3:1). All samples, including blanks, were left on a shaker at 4°C for one hour, centrifuged at 16,000 g for 10 min at 4°C and supernatant was transferred to a fresh tube. Quality control samples were generated by pooling 10 µl of each sample together. Samples were stored at -80°C until further LC-MS analysis.Anopheles gambiaereference compoundsample preparation blankhttps://www.ebi.ac.uk/metabolights/MTBLS11617Barrett Michael.Lee Haines.Dagmara McGuinness.Anna Trett.Clement Regnault.Álvaro Acosta-Serrano.Natalia García.Ghaith Aljayyoussi.Claire Rose.Marcos Sterkel.Didier Leroy.Jeremy Burrows.Giancarlo Biagini.Lakshminarayan Ranganath.Raw data were acquired as described previously (87) and further processed using XCMS and mzMatch (peak-picking and peak matching, respectively).TreatmentReplicateclement.regnault@glasgow.ac.ukMosquitoes were fed a sublethal dose (100 ng/ml) of nitisinone that was added to bovine serum albumin (BSA) reconstituted and filter sterilised in saline (PBS). As protein alone can trigger nitisinone killing in blood-feeding insects when supplied in sugar solutions, BSA was chosen to reduce the complexity of blood-derived metabolites that could obscure the accuracy of the metabolomic assessment for these experiments. In a preliminary experiment, we determined that the mosquito mortality is comparable when 100 ng/ml nitisinone is added to either blood (34% died) or 50 mg/ml BSA (44% died) within a 24 h period. Two cages of mated, Anopheles gambiae Kisumu females were allowed to feed for one hour on 50 mg/ml BSA diluted in sterile PBS, either with nitisinone (100 ng/ml) (treated) or without (control). A fully engorged female A. gambiae mosquito swells with approximately 4 µl of blood (85), thus unfed mosquitoes, even feeding on serum alone, are easy to identify and were immediately removed from the cages. Mosquitoes treated with nitisinone first lose the ability to fly and then rapidly progress to full paralysis and death. The three groups of mosquitoes collected for metabolomic analysis were grouped according to mosquito behaviour: Group A- complete knockdown (mosquitoes were completely paralysed and lying on their backs on the cage floor with only legs twitching), Group B- partial knockdown (mosquitoes could still weakly move and were collected clinging to cage walls and ceiling) and Group C- control (nitisinone -free mosquitoes were collected during flight). Mosquitoes that had died (those with black and bloated abdomens) were not selected for analysis. After 24 h, whole mosquitoes were collected in pools of ten (four technical replicates per group) and snap frozen in liquid nitrogen.MetabolomicsHPPD inhibitorTyrosine Metabolism Pathwayuntargeted metabolitesmalariaectoparasiticideNitisinoneIvermectinHPPD inhibitorTyrosine Metabolism Pathwayuntargeted metabolitesmalariaectoparasiticideNitisinoneIvermectinMetabolomics samples were separated using Q-Exactive Orbitrap mass spectrometer (ThermoFisher) in both positive and negative modes (switching mode) ButenylcarnitineCis-Aconitate3-Hydroxyphenylacetate2-Oxoglutarate(E)-10-Oxo-8-decenoic acidSuberic acidCitrateHomogentisate3-Hydroxyphenyllactate3-HydroxyphenylpyruvateMalateDodecenedioic acid2-Hydroxydecanedioic acidSuccinic acidDecenedioic acid3-Hydroxydodecanedioic acidOne approach to interrupting the transmission of insect-borne diseases that is successfully used in veterinary medicine is exploiting the ability of antiparasitic drugs to make vertebrate blood toxic for blood-feeding insects. Recent studies have identified 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme of the tyrosine detoxification pathway, as essential for hematophagous arthropods to digest their blood meals. Such blood-feeding insects include anopheline mosquitoes, which transmit malaria-causing Plasmodium parasites. A US Food and Drug Administration-approved HPPD enzyme inhibitor called nitisinone is a drug used to treat rare human-inherited disorders of the tyrosine pathway. Here, we demonstrate that feeding human blood containing nitisinone to insectary-reared female Anopheles gambiae mosquitoes was mosquitocidal to both young and old mosquitoes as well as insecticide-resistant Anopheles strains. Pharmacokinetic-pharmacodynamic (PK/PD) modeling of nitisinone's dose-response relationship (when administered at the highest recommended doses for adults and children) demonstrated improved efficacy against mosquitoes compared with the gold standard endectocidal drug, ivermectin. Furthermore, blood samples from individuals with alkaptonuria (a rare genetic metabolic disorder in the tyrosine degradation pathway), who were taking a daily low dose of 2 milligrams of nitisinone, were shown to be lethal to mosquitoes. Thus, inhibiting the Anopheles HPPD enzyme with nitisinone warrants further investigation as a complementary intervention for vector control and the prevention of malaria transmission.Anopheles mosquito survival and pharmacokinetic modeling show the mosquitocidal activity of nitisinone.Haines Lee R LR, Trett Anna A, Rose Clair C, García Natalia N, Sterkel Marcos M, McGuinness Dagmara D, Regnault Clément C, Barrett Michael P MP, Leroy Didier D, Burrows Jeremy N JN, Biagini Giancarlo G, Ranganath Lakshminarayan R LR, Aljayyoussi Ghaith G, Acosta-Serrano Álvaro ÁfalseNitisinone’s mosquitocidal properties hold promise for malaria controlNitisinone’s mosquitocidal properties hold promise for malaria control2025-06-162024-12-13MTBLS11617MTBLC17895MTBLC17295MTBLC86073MTBLC7676MTBLC84842MTBLC167870MTBLC173869MTBLC17445MTBLC30769MTBLC30916MTBLC32805MTBLC6650MTBLC15741MTBLC232842MTBLC89730MTBLC168922MTBLC145961MTBLC89312MTBLC9300MTBLC88785MTBLC4474740138457CHEBI:17895CHEBI:17295CHEBI:86073CHEBI:7676CHEBI:84842CHEBI:167870CHEBI:173869CHEBI:17445CHEBI:30769CHEBI:30916CHEBI:32805CHEBI:6650CHEBI:15741CHEBI:232842CHEBI:89730CHEBI:168922CHEBI:145961CHEBI:89312CHEBI:9300CHEBI:88785CHEBI:44747