MetaboLights

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ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/m_Lipidomics_NEG_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/m_DMEM_Metabolomics_neg_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/m_DMEM_Metabolomics_pos_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/m_DMEM_Metabolomics_GC_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/m_Lipidomics_POS_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/s_MTBLS14351.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/a_MTBLS14351_LC-MS_positive_normal-phase.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/a_MTBLS14351_LC-MS_negative_normal-phase.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/a_MTBLS14351_LC-MS_positive_normal-phase-1.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/a_MTBLS14351_GC-MS_alternating_normal-phase.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/a_MTBLS14351_LC-MS_negative_normal-phase-1.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351/i_Investigation.txtprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14351Lipid MAPS and LipidBlast databases were used for tagerted lipidomics analysis.MetaboLightsPublicGas Chromatography MS - alternating - normal-phaseLiquid Chromatography MS - positive - normal-phaseLiquid Chromatography MS - negative - normal-phaseAnalysis of GC-MS was performed on an Agilent 8890-5977B system equipped with a DB-5MS column. Helium (1.0 mL/min) served as the carrier gas, and data were acquired via an EI source in full-scan mode (m/z 50–500). Analysis of LC-MS utilized a Waters ACQUITY UPLC I-Class plus system coupled to a Thermo Q-Exactive Plus mass spectrometer, using an HSS T3 column operated in Full-scan/HCD MS/MS mode.Metabolic plasticity of lipid storage and utilization governs fungal persister formation within macrophages.Yi LiPeking union medical college hospitalWhole Organismmass spectrometry assayA unified methanol-chloroform-water method was employed for metabolite extraction, with L-2-chlorophenylalanine added as an internal standard. For LC-MS preparation, the supernatant was vacuum-dried, reconstituted in methanol-water, and filtered through an organic membrane prior to injection. For GC-MS preparation, dried supernatants underwent a two-step derivatization process: methoximation followed by silylation using BSTFA. Pooled samples were used as control.Candida glabratahttps://www.ebi.ac.uk/metabolights/MTBLS14351Su Yanyu.Li Yingxing.Yi Li. Peking Union Medical College Hospital. No.1 Shuaifuyuan Wangfujing, Dongcheng district, Beijing, China. liyi67@pumch.cn.Raw data were pre-processed using Progenesis QI V2.3, with metabolites identified against the HMDB and Lipidmaps databases. Differential metabolites were screened using OPLS-DA models (VIP > 1.0, p < 0.05). Genotypeliyi67@pumch.cnC. glabrata strains were grown in YPD broth for 13 h to reach stationary phase. Cells were harvested, washed twice with PBS, and inoculated at a target density of 108 cells into 10 mL of DMEM. After 3 h of incubation at 37°C, cells were collected by centrifugation. Following quantification, samples were flash-frozen in liquid nitrogen and stored at -80°C until further processing. Six biological replicates were processed for each experimental group. MetabolomicsMetabolomicsMulti-omics studyWaters ACQUITY UPLC I-Class PLUS Systemtargeted analysisuntargeted analysisOrbitrap Exploris 120Candida glabrataThermo Scientific Q Exactive PlusWhole Organismuntargeted metabolite profilingfungal metaboliteAB SCIEX QTRAP 6500+SCIEX ExionLC ACThermo Scientific TRACE 1310 GCexperimental blankMetabolomicsMulti-omics studyWaters ACQUITY UPLC I-Class PLUS Systemtargeted analysisuntargeted analysisOrbitrap Exploris 120Candida glabrataThermo Scientific Q Exactive PlusWhole Organismuntargeted metabolite profilingfungal metaboliteAB SCIEX QTRAP 6500+SCIEX ExionLC ACThermo Scientific TRACE 1310 GCexperimental blankAnalysis of GC-MS was performed on an Agilent 8890-5977B system equipped with a DB-5MS column. Helium (1.0 mL/min) served as the carrier gas, and data were acquired via an EI source in full-scan mode (m/z 50–500). Analysis of LC-MS utilized a Waters ACQUITY UPLC I-Class plus system coupled to a Thermo Q-Exactive Plus mass spectrometer, using an HSS T3 column operated in Full-scan/HCD MS/MS mode.PE(18:1/18:1)PG(18:0/18:1)PE(16:0/22:6)PS(18:0/22:6)LPE(18:2)LPE(16:0)PA(18:0/18:1)PC(16:0/18:2)LPS(16:1)PC(16:0/16:0)PE(16:0/20:4)FA(14:0)PC(16:1/20:4)PE(14:0/16:1)PE(16:1/20:1)PC(18:0/22:5)PE(18:1/20:4)FA(20:0)PI(16:0/16:1)PC(18:1/20:1)LPE(16:1)PS(16:0/16:1)PC(16:1/18:1)PA(18:0/18:0)LPC(20:5)LPS(16:0)PC(16:0/16:1)PE(18:1/22:6)PI(18:0/20:3)PC(16:1/20:5)PG(16:0/20:0)PC(14:0/14:0)PC(18:1/18:2)LPE(18:0)PA(16:0/22:6)PE(16:0/18:1)PC(16:0/18:0)PI(18:0/20:4)LPC(14:1)PE(16:1/20:3)LPE(20:4)PC(16:1/20:2)PE(16:1/22:4)PE(18:1/18:2)PI(18:0/18:1)PE(16:0/22:5)PS(16:0/18:1)FA(18:0)PC(16:0/22:6)LPE(18:1)LPS(18:0)PI(18:1/20:4)PE(16:0/18:0)PC(16:0/20:4)PC(16:0/18:1)FA(15:0)PC(16:1/20:3)PE(18:1/20:1)PE(18:0/20:4)PE(16:1/18:1)PG(16:0/18:1)LPE(17:1)PC(16:1/16:1)PE(16:0/16:1)LPA(18:1)PC(16:0/20:3)PA(16:0/18:1)Cholesterol sulfateLPC(16:1)PS(18:0/16:1)PC(14:0/16:0)PE(18:0/22:6)LPG(18:0)PS(16:0/22:5)PC(18:1/20:5)LPI(16:0)PE(18:0/18:1)PC(18:0/18:2)PE(16:0/16:0)LPE(22:5)LPA(18:0)PS(18:1/18:1)PC(16:1/20:1)PC(14:0/16:1)LPE(20:3)LPG(18:1)LPC(18:2)PE(16:1/20:4)LPE(14:0)PI(16:0/20:4)PE(18:1/20:3)PE(18:1/22:5)PC(16:1/18:2)PC(18:0/18:1)PE(16:1/16:1)PC(16:0/20:1)PG(16:0/16:0)FA(16:0)PA(18:0/22:6)PE(14:0/18:1)LPG(16:0)LPE(14:1)PE(18:1/20:2)PI(16:0/18:1)PS(18:0/20:3)PA(18:1/22:6)PE(18:0/20:3)PS(18:0/18:1)PC(18:1/20:3)PC(18:1/22:5)PE(16:1/18:2)PS(18:0/22:5)PC(18:0/18:0)PS(18:1/22:4)LPI(18:0)PG(16:0/16:1)PS(16:0/20:0)PC(14:0/18:1)PE(18:0/22:5)LPG(16:1)falseMetabolic plasticity of lipid storage and utilization governs fungal persister formation within macrophagesThe ability of Candida glabrata to survive within macrophages creates a reservoir for recurrent infections and antifungal failure, yet the underlying mechanisms remain elusive. Here, using a host-mimicking in vitro evolution model, we identify asparagine synthetase (ASN2) as a critical genetic determinant of intracellular persistence. We show that ASN2 deficiency confers a significant fitness advantage in vivo under echinocandin pressure by inducing a state of metabolic dormancy. Integrated multi-omics analyses reveal that asparagine starvation in ΔASN2 mutants causes a bottleneck in the tricarboxylic acid (TCA) cycle, rewiring carbon flux toward the accumulation of intracellular lipids. This lipid accumulation strategy is coupled with growth arrest, thereby protecting the fungus from echinocandins. In stark contrast, we find that wild-type prototrophic persisters rely on the mobilization of lipid reserves via peroxisomal fatty acid β-oxidation to fuel their survival. Disruption of ACAA1, encoding a peroxisomal 3-ketoacyl-CoA thiolase, impairs lipid utilization and attenuates the prototrophic persister state. Our study delineates a metabolic bifurcation where C. glabrata exploits either passive lipid storage for dormancy or active lipid oxidation for endurance to survive the hostile phagosomal environment and echinocandin pressure, highlighting metabolic checkpoints as potential therapeutic 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