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Yibmantasiri P, et al.  (2012) Molecular basis for fungicidal action of neothyonidioside, a triterpene glycoside from the sea cucumber, Australostichopus mollis. Mol Biosyst 8(3):902-12

Abstract: Neothyonidioside is a triterpene glycoside (TG) isolated from the sea cucumber, Australostichopus mollis, that is potently cytotoxic to S. cerevisiae, but does not permeabilize cellular membranes. We mutagenized S. cerevisiae and isolated a neothionidioside-resistant (neo(R)) strain. Using synthetic genetic array mapping and sequencing, we identified NCP1 as the resistance locus. Quantitative HPLC revealed that neo(R)/ncp1 mutants have reduced ergosterol content. Ergosterol added to growth media reversed toxicity, demonstrating that neothionidioside binds directly to ergosterol, similar to the polyene natamycin. Ergosterol synthesis inhibitors ketoconazole and atorvastatin conferred resistance to neothionidioside in a dose-dependent manner showing that a threshold ergosterol concentration is required for toxicity. A genome-wide screen of deletion mutants against neothionidioside revealed hypersensitivity of many of the component genes in the ESCRT complexes relating to multivesicular body formation. Confocal microscopy of cells stained with a vital dye showed blockage at this step. Thus, we propose neothionidioside may affect membrane curvature and fusion capability in the endosome-vacuole pathway.

Status: Published Type: Journal Article PubMed ID: 22271309

Topics addressed in this paper

Number of different genes curated to this paper: 88

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
ALF1 ALG3 ALG5 ALG6 ALG8 APL1 APM3 APN1 ARP6 BST1
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Infection and Antifungals blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Large-scale phenotype analysis yg ball
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Omics yg ball
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Topics Genes linked to topics (#11 - 20 )
CAP1 CIN2 CKA2 CWH41 DCW1 DFG5 ECM33 ELM1 END3 ERG4
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Infection and Antifungals blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#21 - 30 )
ERV14 FAT1 FEN1 FUM1 GVP36 HXK2 KRE1 LCB3 LDB16 LDB17
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Infection and Antifungals blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#31 - 40 )
MAK10 MAK3 MDM31 MED1 MET32 MMS1 MRPL32 MTO1 MUD1 NBP2
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Infection and Antifungals blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#41 - 50 )
NCP1 OPI1 OSH3 OST3 PAP2 PMP3 PMR1 PMT1 PPM1 ROT1
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DNA/RNA Sequence Features blue ball
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Topics Genes linked to topics (#51 - 60 )
RPL31A RPL35A RPS19A RRD2 RVS161 RVS167 SAC7 SCS2 SIF2 SIP3
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Infection and Antifungals blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Mutants/Phenotypes blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#61 - 70 )
SLG1 SMI1 SNF6 SNF7 SNF8 SSH1 SSO1 STP22 SUR2 SVF1
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Infection and Antifungals blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#71 - 80 )
SWI4 URE2 VAM7 VAN1 VPS17 VPS20 VPS25 VPS27 VPS28 VPS36
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Infection and Antifungals blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball

Topics Genes linked to topics (#81 - 88 )
VPS4 VPS41 VPS51 VPS52 VPS9 YIM1 YSP1 YSP2
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Infection and Antifungals blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Mutants/Phenotypes blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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