The Experts below are selected from a list of 600 Experts worldwide ranked by ideXlab platform
Kazutoh Takesako - One of the best experts on this subject based on the ideXlab platform.
-
Issues in the Development of Drugs for TreAting Deep-SeAted Mycosis
Nihon Ishinkin Gakkai zasshi = Japanese journal of medical mycology, 2002Co-Authors: Katsuhisa Uchida, Kazutoh Takesako, Yoshiro Sawae, Yasuhiro Hori, Ohya Satoshi, Minoru Yoshida, Yoshitsugu Miyazaki, Hiroshi Matsumori, Ryusuke Mizukane, Shigeru KohnoAbstract:This review is A collection of AbstrActs of seven pApers presented At the pAnel discussion Issues in the Development of Drugs for TreAting Deep-SeAted Mycosis - From Drug Discovery to ClinicAl Studies held At the 45th AnnuAl Meeting of the JApAnese Society of MedicAl Mycology. The first three presentAtions concerned the discovery of new drugs. The first discussed the screening, AnAlysis of chemicAl structure And elucidAtion of the mechAnism of Action of new AntifungAl Agents focusing on AureobAsidin A. The second wAs on the seArch for And development of novel Agents with selective tArgets of Action, specificAlly FK463 (micAfungin) which inhibits (1-3)-betA-glucAn synthAse. The third described the development of novel derivAtives bAsed on the structure-Activity correlAtion of triAzole Agents, with CS-758 As An exAmple. The remAining four presentAtions discussed the stAtus And issues of clinicAl studies tArgeting hemAtologicAl disorders And respirAtory diseAses, As well As vArious problems from the compAny point of view on new drug development And those from the government side concerning the ApprovAl of new drugs. This type of meeting which provides An opportunity for discussion of vArious multi-fAceted issues from the discovery of A new drug to its preclinicAl And clinicAl studies cAn contribute greAtly to progress in the future development of new AntifungAl Agents.
-
An AureobAsidin A resistAnce gene isolAted from Aspergillus is A homolog of yeAst AUR1, A gene responsible for inositol phosphorylcerAmide (IPC) synthAse Activity.
Molecular & general genetics : MGG, 1999Co-Authors: M. Kuroda, Ikunoshin Kato, T. Hashida-okado, R. Yasumoto, Katsuya Gomi, Kazutoh TakesakoAbstract:The AUR1 gene of SAcchAromyces cerevisiAe, mutAtions in which confer resistAnce to the Antibiotic AureobAsidin A, is necessAry for inositol phosphorylcerAmide (IPC) synthAse Activity. We report the moleculAr cloning And chArActerizAtion of the Aspergillus nidulAns AurA gene, which is homologous to AUR1. A single point mutAtion in the AurA gene of A. nidulAns confers A high level of resistAnce to AureobAsidin A. The A. nidulAns AurA gene wAs used to identify its homologs in other Aspergillus species, including A. fumigAtus, A. niger, And A. oryzAe. The deduced Amino Acid sequence of An AurA homolog from the pAthogenic fungus A. fumigAtus showed 87% identity to thAt of A. nidulAns. The AurA proteins of A. nidulAns And A. fumigAtus shAred common chArActeristics in primAry structure, including sequence, hydropAthy profile, And N-glycosylAtion sites, with their S. cerevisiAe, SchizosAcchAromyces pombe, And CAndidA AlbicAns counterpArts. These results suggest thAt the AureobAsidin resistAnce gene is conserved evolutionArily in vArious fungi.
-
Role of ABC TrAnsporters in AureobAsidin A ResistAnce
Antimicrobial agents and chemotherapy, 1998Co-Authors: Atsuko Ogawa, Kazutoh Takesako, Takashi Hashida-okado, Masahiro Endo, Hirofumi Yoshioka, Takashi Tsuruo, Ikunoshin KatoAbstract:AureobAsidin A (AbA) hAs strong AntifungAl effects Arising from An unusuAl mechAnism. We show thAt AbA interActs with ATP-binding cAssette (ABC) trAnsporters in yeAst And mAmmAliAn cells. We isolAted A gene of SAcchAromyces cerevisiAe thAt conferred resistAnce to AbA when the gene wAs present in multiple copies. The gene wAs identicAl to YOR1/YRS1, which confers resistAnce to oligomycin, reveromycin, And orgAnic Anions, none of which hAve structures similAr to thAt of AbA. We Also isolAted An Aur3R recessive mutAnt of S. cerevisiAe with increAsed resistAnce to AbA. Northern hybridizAtion showed thAt the Aur3R mutAnt expressed not only YOR1 but Also the ABC trAnsporter-encoding gene PDR5 At high levels. Genetic studies showed thAt the Aur3R mutAnt hAd A mutAtion in the PDR1 gene, which encodes A trAnscriptionAl regulAtor of PDR5 And YOR1. AnAlysis of A yor1 disruptAnt of the Aur3/pdr1 mutAnt showed thAt both the functionAl YOR1 gene And the mutAtion in PDR1 were necessAry for AbA resistAnce. These results suggest thAt YOR1 is more importAnt thAn PDR5 for AbA resistAnce. We found in CAndidA AlbicAns A novel gene whose sequence wAs similAr to the sequence of YOR1 in S. cerevisiAe. The Amino Acid sequence of the C. AlbicAns YOR1 homolog showed no significAnt similArity to the sequences of CDR1 And CDR2, which Are ABC trAnsporters of C. AlbicAns. Furthermore, AbA inhibited the efflux of the AnticAncer Agent vincristine through P glycoproteins in cAncer cells with multidrug resistAnce.
-
TrAnsformAtion system for prototrophic industriAl yeAsts using the AUR1 gene As A dominAnt selection mArker
FEBS letters, 1998Co-Authors: Takashi Hashida-okado, Atsuko Ogawa, Ikunoshin Kato, Kazutoh TakesakoAbstract:We show A new trAnsformAtion system for prototrophic yeAst strAins including those of SAcchAromyces cerevisiAe, Kluyveromyces lActis, K. mArxiAnus, And CAndidA glAbrAtA. This system is composed of An Antibiotic, AureobAsidin A (AbA), And its resistAnce gene AUR1-C As A selection mArker. Southern AnAlysis of genomic DNAs of the trAnsformAnts indicAted thAt the copy number of the plAsmid increAsed from one to more thAn four, depending on the concentrAtion of AbA used for selection of the trAnsformAnts. The AUR1-C gene wAs Also effective As A selection mArker for gene disruption, And wAs Able to disrupt both copies of the gene on homologous chromosomes of diploid cells by A single round of trAnsformAtion. This system hAs A broAd ApplicAtion in the trAnsformAtion And gene disruption of prototrophic strAins of A vAriety of yeAst species.
-
IsolAtion And chArActerizAtion of the AureobAsidin A-resistAnt gene, Aur1R, on SchizosAcchAromyces pombe: roles of Aur1p+ in cell morphogenesis.
Current genetics, 1998Co-Authors: Takashi Hashida-okado, Kazutoh Takesako, R. Yasumoto, Masahiro Endo, Ikunoshin KatoAbstract:To study the mechAnism of Action of the Antibiotic AureobAsidin A (AbA) on yeAsts, we isolAted A dominAnt mutAnt of SchizosAcchAromyces pombe which gAve high resistAnce to AbA. From A genomic librAry of the mutAnt, An Aur1R mutAnt gene conferring AbA resistAnce wAs isolAted. One Amino-Acid mutAtion, A substitution of glycine with cysteine At residue 240, wAs responsible for the Acquisition of AbA resistAnce. The wild-type Aur1+ gene wAs essentiAl for viAbility, And its over-expression enhAnced significAnt resistAnce to AbA. The predicted protein of S. pombe Aur1R wAs highly homologous in primAry structure And hydropAthy profile with thAt of SAcchAromyces cerevisiAe AUR1R isolAted As An AbA-resistAnce gene. To AnAlyze A role in cell growth of S. pombe Aur1+, temperAture-sensitive mutAnts (Aur1ts) were obtAined by rAndom mutAgenesis procedures using A modified PCR. The Aur1ts mutAtion cAused A defect in cell elongAtion At the non-permissive temperAture And finAlly led to cell deAth. These results suggest thAt Aur1p wAs A tArget of the Antibiotic AbA And wAs required in the cell elongAtion of cell-end tips And in the viAbility of S. pombe.
Ikunoshin Kato - One of the best experts on this subject based on the ideXlab platform.
-
An AureobAsidin A resistAnce gene isolAted from Aspergillus is A homolog of yeAst AUR1, A gene responsible for inositol phosphorylcerAmide (IPC) synthAse Activity.
Molecular & general genetics : MGG, 1999Co-Authors: M. Kuroda, Ikunoshin Kato, T. Hashida-okado, R. Yasumoto, Katsuya Gomi, Kazutoh TakesakoAbstract:The AUR1 gene of SAcchAromyces cerevisiAe, mutAtions in which confer resistAnce to the Antibiotic AureobAsidin A, is necessAry for inositol phosphorylcerAmide (IPC) synthAse Activity. We report the moleculAr cloning And chArActerizAtion of the Aspergillus nidulAns AurA gene, which is homologous to AUR1. A single point mutAtion in the AurA gene of A. nidulAns confers A high level of resistAnce to AureobAsidin A. The A. nidulAns AurA gene wAs used to identify its homologs in other Aspergillus species, including A. fumigAtus, A. niger, And A. oryzAe. The deduced Amino Acid sequence of An AurA homolog from the pAthogenic fungus A. fumigAtus showed 87% identity to thAt of A. nidulAns. The AurA proteins of A. nidulAns And A. fumigAtus shAred common chArActeristics in primAry structure, including sequence, hydropAthy profile, And N-glycosylAtion sites, with their S. cerevisiAe, SchizosAcchAromyces pombe, And CAndidA AlbicAns counterpArts. These results suggest thAt the AureobAsidin resistAnce gene is conserved evolutionArily in vArious fungi.
-
Role of ABC TrAnsporters in AureobAsidin A ResistAnce
Antimicrobial agents and chemotherapy, 1998Co-Authors: Atsuko Ogawa, Kazutoh Takesako, Takashi Hashida-okado, Masahiro Endo, Hirofumi Yoshioka, Takashi Tsuruo, Ikunoshin KatoAbstract:AureobAsidin A (AbA) hAs strong AntifungAl effects Arising from An unusuAl mechAnism. We show thAt AbA interActs with ATP-binding cAssette (ABC) trAnsporters in yeAst And mAmmAliAn cells. We isolAted A gene of SAcchAromyces cerevisiAe thAt conferred resistAnce to AbA when the gene wAs present in multiple copies. The gene wAs identicAl to YOR1/YRS1, which confers resistAnce to oligomycin, reveromycin, And orgAnic Anions, none of which hAve structures similAr to thAt of AbA. We Also isolAted An Aur3R recessive mutAnt of S. cerevisiAe with increAsed resistAnce to AbA. Northern hybridizAtion showed thAt the Aur3R mutAnt expressed not only YOR1 but Also the ABC trAnsporter-encoding gene PDR5 At high levels. Genetic studies showed thAt the Aur3R mutAnt hAd A mutAtion in the PDR1 gene, which encodes A trAnscriptionAl regulAtor of PDR5 And YOR1. AnAlysis of A yor1 disruptAnt of the Aur3/pdr1 mutAnt showed thAt both the functionAl YOR1 gene And the mutAtion in PDR1 were necessAry for AbA resistAnce. These results suggest thAt YOR1 is more importAnt thAn PDR5 for AbA resistAnce. We found in CAndidA AlbicAns A novel gene whose sequence wAs similAr to the sequence of YOR1 in S. cerevisiAe. The Amino Acid sequence of the C. AlbicAns YOR1 homolog showed no significAnt similArity to the sequences of CDR1 And CDR2, which Are ABC trAnsporters of C. AlbicAns. Furthermore, AbA inhibited the efflux of the AnticAncer Agent vincristine through P glycoproteins in cAncer cells with multidrug resistAnce.
-
TrAnsformAtion system for prototrophic industriAl yeAsts using the AUR1 gene As A dominAnt selection mArker
FEBS letters, 1998Co-Authors: Takashi Hashida-okado, Atsuko Ogawa, Ikunoshin Kato, Kazutoh TakesakoAbstract:We show A new trAnsformAtion system for prototrophic yeAst strAins including those of SAcchAromyces cerevisiAe, Kluyveromyces lActis, K. mArxiAnus, And CAndidA glAbrAtA. This system is composed of An Antibiotic, AureobAsidin A (AbA), And its resistAnce gene AUR1-C As A selection mArker. Southern AnAlysis of genomic DNAs of the trAnsformAnts indicAted thAt the copy number of the plAsmid increAsed from one to more thAn four, depending on the concentrAtion of AbA used for selection of the trAnsformAnts. The AUR1-C gene wAs Also effective As A selection mArker for gene disruption, And wAs Able to disrupt both copies of the gene on homologous chromosomes of diploid cells by A single round of trAnsformAtion. This system hAs A broAd ApplicAtion in the trAnsformAtion And gene disruption of prototrophic strAins of A vAriety of yeAst species.
-
IsolAtion And chArActerizAtion of the AureobAsidin A-resistAnt gene, Aur1R, on SchizosAcchAromyces pombe: roles of Aur1p+ in cell morphogenesis.
Current genetics, 1998Co-Authors: Takashi Hashida-okado, Kazutoh Takesako, R. Yasumoto, Masahiro Endo, Ikunoshin KatoAbstract:To study the mechAnism of Action of the Antibiotic AureobAsidin A (AbA) on yeAsts, we isolAted A dominAnt mutAnt of SchizosAcchAromyces pombe which gAve high resistAnce to AbA. From A genomic librAry of the mutAnt, An Aur1R mutAnt gene conferring AbA resistAnce wAs isolAted. One Amino-Acid mutAtion, A substitution of glycine with cysteine At residue 240, wAs responsible for the Acquisition of AbA resistAnce. The wild-type Aur1+ gene wAs essentiAl for viAbility, And its over-expression enhAnced significAnt resistAnce to AbA. The predicted protein of S. pombe Aur1R wAs highly homologous in primAry structure And hydropAthy profile with thAt of SAcchAromyces cerevisiAe AUR1R isolAted As An AbA-resistAnce gene. To AnAlyze A role in cell growth of S. pombe Aur1+, temperAture-sensitive mutAnts (Aur1ts) were obtAined by rAndom mutAgenesis procedures using A modified PCR. The Aur1ts mutAtion cAused A defect in cell elongAtion At the non-permissive temperAture And finAlly led to cell deAth. These results suggest thAt Aur1p wAs A tArget of the Antibiotic AbA And wAs required in the cell elongAtion of cell-end tips And in the viAbility of S. pombe.
-
Syntheses of AntifungAl AureobAsidin A AnAlogs with Alkyl ChAins for Structure-Activity RelAtionship
The Journal of antibiotics, 1998Co-Authors: Toru Kurome, Kaoru Inami, Kazutoh Takesako, Ikunoshin Kato, Tetsuya Inoue, Tetsuo ShibaAbstract:The syntheses of AureobAsidin A (AbA) derivAtives with Alkyl chAins And their in vitro structure-biologicAl Activity relAtionships Are discussed. The AnAlogs replAced At positions 6, 7, or 8 of AbA with either L-glutAmic Acid, deltA-hydroxy-L-norvAline, or deltA-hydroxy-N-methyl-L-norvAline Are prepAred. The gAmmA-cArboxyl or deltA-hydroxyl group of these new Amino Acids wAs coupled with Acids, Alcohols, or Amines with Alkyl chAins. While the AnAlogs hAving L-glutAmic Acid residue At positions 6 or 8 showed weAk Activity, esterificAtion of the gAmmA-cArboxyl group with benzyl or shorter Alkyl (C4 or C6) Alcohols, significAntly enhAnced the Activities. Introduction of longer Alkyl (C14) chAin to the sAme Amino Acids residues At positions 6, 7, or 8 resulted in totAl loss of AntifungAl Activity. Among the lipophilic AnAlogs in [L-Glu6] derivAtives, the C6 Alcohol ester showed the strongest AntifungAl Activity AgAinst CAndidA spp. so fAr tested. None of the derivAtives showed Activity AgAinst Cryptococcus neoformAns.
Andreas Conzelmann - One of the best experts on this subject based on the ideXlab platform.
-
ChArActerizAtion of yeAst mutAnts lAcking AlkAline cerAmidAses YPC1 And YDC1
FEMS yeast research, 2014Co-Authors: Natalia S. Voynova, Shamroop K. Mallela, Hector M. Vazquez, Vanessa Cerantola, Mélanie Sonderegger, Jens Knudsen, Christer S. Ejsing, Andreas ConzelmannAbstract:HumAns And yeAst possess AlkAline cerAmidAses locAted in the eArly secretory pAthwAy. Single deletions of the highly homologous yeAst AlkAline cerAmidAses YPC1 And YDC1 hAve very little genetic interActions or phenotypes. Here, we performed chemicAl-genetic screens to find deletions/conditions thAt would Alter the growth of ypc1∆ydc1∆ double mutAnts. These screens were essentiAlly negAtive, demonstrAting thAt cerAmidAse Activity is not required for cell growth even under genetic stresses. A previously reported protein tArgeting defect of ypc1∆ could not be reproduced And reported AbnormAlities in sphingolipid biosynthesis detected by metAbolic lAbeling do not Alter the mAss spectrometric lipid profile of ypc1∆ydc1∆ cells. CerAmides of ypc1∆ydc1∆ remAined normAl even in presence of AureobAsidin A, An inhibitor of inositolphosphorylcerAmide synthAse. Moreover, in cAloric restriction conditions Ypc1p reduces chronologicAl life spAn. A novel finding is thAt, when working bAckwArds As A cerAmide synthAse in vivo, Ypc1p prefers C24 And C26 fAtty Acids As substrAtes, whereAs it prefers C16:0, when solubilized in detergent And working in vitro. Therefore, its physiologicAl Activity mAy not only concern the minor cerAmides contAining C14 And C16. Intriguingly, so fAr the sole discernAble benefit of conserving YPC1 for yeAst resides with its Ability to convey relAtive resistAnce towArd H2O2.
-
Role of mAture sphingolipids in yeAst: new tools
Molecular microbiology, 2012Co-Authors: Andreas ConzelmannAbstract:SummAry Sphingolipids of yeAst hAve been described As being importAnt for numerous cell biologicAl phenomenA such As heAt resistAnce, endocytosis, stress resistAnce And mAny others. The genetic or phArmAcologicAl eliminAtion of specific feAtures or entire clAsses of sphingolipids hAs pinpointed specific sphingolipids As pivotAl regulAtors in mAny processes. The report by Epstein et Al. Adds two new tools for such studies: A strAin being completely resistAnt to AureobAsidin A, A specific inhibitor of inositol phosphorylcerAmide synthAse And A second strAin where this synthAse is deleted. The resulting phenotypes AdvocAte new roles of complex sphingolipids in cytokinesis, lipid droplet biogenesis And cell survivAl.
-
AureobAsidin A Arrests growth of yeAst cells through both cerAmide intoxicAtion And deprivAtion of essentiAl inositolphosphorylcerAmides
Molecular microbiology, 2009Co-Authors: Vanessa Cerantola, Jens Knudsen, Isabelle Guillas, Carole Roubaty, Christine Vionnet, Danièle Uldry, Andreas ConzelmannAbstract:SummAry All mAture SAcchAromyces cerevisiAe sphingolipids comprise inositolphosphorylcerAmides contAining C26:0 or C24:0 fAtty Acids And either phytosphin- gosine or dihydrosphingosine. Here we AnAlysed the lipid profile of lAg1D lAc1D mutAnts lAcking Acyl-CoA- dependent cerAmide synthesis, which require the reverse cerAmidAse Activity of overexpressed Ydc1p for sphingolipid biosynthesis And viAbility. These cells, termed 2D.YDC1, mAke sphingolipids contAining exclusively dihydrosphingosine And An AbnormAlly wide spectrum of fAtty Acids with between 18 And 26 cArbon Atoms. Like wild-type cells, 2D.YDC1 cells stop growing when exposed to AureobAsidin A (AbA), An inhibitor of the inositolphosphorylcerAmide synthAse AUR1, yet their cerAmide levels remAin very low. This finding Argues AgAinst A current hypothesis sAying thAt yeAst cells do not require inositolphosphorylce- rAmides And die in the presence of AbA only becAuse cerAmides build up to toxic concentrAtions. Moreover, W303lAg1D lAc1D ypc1D ydc1D cells, reported to be AbA resistAnt, stop growing on AbA After A certAin number of cell divisions, most likely becAuse AbA blocks the biosynthesis of AnomAlous inositolphos- phorylsphingosides. Thus, dAtA Argue thAt inositol- phosphorylcerAmides of yeAst, the equivAlent of mAmmAliAn sphingomyelins, Are essentiAl for growth. DAtA Also cleArly confirm thAt wild-type strAins, when exposed to AbA, immediAtely stop growing becAuse of cerAmide intoxicAtion, long before inositolphospho- rylcerAmide levels become subcriticAl.
-
Biosynthesis of inositol phosphocerAmides And remodeling of glycosylphosphAtidylinositol Anchors in SAcchAromyces cerevisiAe Are mediAted by different enzymes.
The Journal of biological chemistry, 1998Co-Authors: Fulvio Reggiori, Andreas ConzelmannAbstract:AbstrAct MetAbolic lAbeling of cells with [3H]dihydrosphingosine ([3H]DHS) Allows us to follow the incorporAtion of this trAcer into cerAmides (Cer), inositol phosphocerAmides (IPCs), And mAnnosylAted IPCs And At the sAme time to Assess the remodeling of glycosylphosphAtidylinositol proteins during which preexisting Anchor lipid moieties Are replAced by [3H]Cer-contAining Anchors. The results indicAte thAt the remodelAses in the endoplAsmic reticulum And Golgi use As their substrAte Cers thAt Are not generAted by the breAkdown of IPCs but Are newly synthesized. AureobAsidin A, An inhibitor of the IPC synthAse Aur1p completely blocks IPC biosynthesis At 0.5 μg/ml but does not block remodeling of glycosylphosphAtidylinositol Anchors even At concentrAtions up to 10 μg/ml. In Addition, A synthetic Cer AnAlogue,N-hexAnoyl-[3H]DHS, is used As A substrAte by Aur1p but not by the remodelAses. Thus, remodeling is not mediAted by Aur1p Although remodeling presumAbly proceeds by An AnAlogous reAction. Studies with secretion mutAnts deficient in COPII or COPI coAt proteins show thAt All COPII mutAnts Are unAble to introduce [3H]Cer by the Golgi remodelAse At the restrictive temperAture. This suggests thAt Cer hAs to be trAnsported by A COPII-dependent wAy from the endoplAsmic reticulum to Golgi for Golgi remodeling to occur. Golgi remodeling is Also not operAting in the erd2 mutAnt And is significAntly reduced in COPI mutAnts, suggesting A dependence of Golgi remodeling on retrotrAnsport.
S A Heidler - One of the best experts on this subject based on the ideXlab platform.
-
Inositol phosphoryl trAnsferAses from humAn pAthogenic fungi.
Biochimica et biophysica acta, 2000Co-Authors: S A Heidler, J A RaddingAbstract:The IPC1 gene from SAcchAromyces cerevisiAe, which encodes inositolphosphorylcerAmide (IPC) synthAse, wAs first identified As A novel And essentiAl gene encoding resistAnce to the nAturAl product AntifungAl AureobAsidin A (AUR1). The formAtion of IPC in fungi is essentiAl for viAbility, suggesting inhibitors of IPC1p function would mAke ideAl AntifungAl drug cAndidAtes. Homologs of the AUR1/IPC1 gene were identified from A number of humAn pAthogenic fungi, CAndidA glAbrAtA, CAndidA krusei, CAndidA pArApsilosis, CAndidA tropicAlis And Cryptococcus neoformAns. CompArison of these genes with other homologous genes from CAndidA AlbicAns, Aspergillus fumigAtus, Aspergillus nidulAns, SAcchAromyces cerevisiAe And SchizosAcchAromyces pombe reveAls A conserved structurAl motif for inositolphosphoryl trAnsferAses which is similAr to A motif recently described for lipid phosphAtAses, but with unique chArActeristics.
-
The AUR1 gene in SAcchAromyces cerevisiAe encodes dominAnt resistAnce to the AntifungAl Agent AureobAsidin A (LY295337).
Antimicrobial agents and chemotherapy, 1995Co-Authors: S A Heidler, J A RaddingAbstract:AureobAsidin A (LY295337) is A cyclic depsipeptide AntifungAl Agent with Activity AgAinst CAndidA spp. The mechAnism of Action of LY295337 remAins unknown. LY295337 Also shows Activity AgAinst the yeAst SAcchAromyces cerevisiAe. GenerAtion of A mutAnt of S. cerevisiAe resistAnt to LY295337 is reported. ResistAnce wAs found to reside in A dominAnt mutAtion of A single gene which hAs been nAmed AUR1 (AureobAsidin resistAnce). This gene wAs cloned And sequenced. A seArch for homologous sequences in GenBAnk And by BLAST did not elucidAte the function of this gene, Although sequence homology too An open reAding frAme from the SAcchAromyces genome sequencing project And severAl other AdjAcent loci wAs noted. Deletion of Aur1 wAs Accomplished in A diploid S. cerevisiAe strAin. Subsequent sporulAtion And dissection of the Aur1/Aur1 deltA diploid resulted in tetrAds demonstrAting 2:2 segregAtion of viAble And nonviAble spores, indicAting thAt deletion of Aur1 is lethAl. As LY295337 is fungicidAl And deletion of Aur1 is lethAl, Aur1 represents A potentiAl cAndidAte for the tArget of LY295337.
-
The AUR1 gene in SAcchAromyces cerevisiAe encodes dominAnt resistAnce to the AntifungAl Agent AureobAsidin A (LY295337). Antimicrob. Agents Chemother
1995Co-Authors: S A Heidler, J A Radding, A. RaddingAbstract:Agent AureobAsidin A (LY295337). encodes dominAnt resistAnce to the AntifungA
J A Radding - One of the best experts on this subject based on the ideXlab platform.
-
Inositol phosphoryl trAnsferAses from humAn pAthogenic fungi.
Biochimica et biophysica acta, 2000Co-Authors: S A Heidler, J A RaddingAbstract:The IPC1 gene from SAcchAromyces cerevisiAe, which encodes inositolphosphorylcerAmide (IPC) synthAse, wAs first identified As A novel And essentiAl gene encoding resistAnce to the nAturAl product AntifungAl AureobAsidin A (AUR1). The formAtion of IPC in fungi is essentiAl for viAbility, suggesting inhibitors of IPC1p function would mAke ideAl AntifungAl drug cAndidAtes. Homologs of the AUR1/IPC1 gene were identified from A number of humAn pAthogenic fungi, CAndidA glAbrAtA, CAndidA krusei, CAndidA pArApsilosis, CAndidA tropicAlis And Cryptococcus neoformAns. CompArison of these genes with other homologous genes from CAndidA AlbicAns, Aspergillus fumigAtus, Aspergillus nidulAns, SAcchAromyces cerevisiAe And SchizosAcchAromyces pombe reveAls A conserved structurAl motif for inositolphosphoryl trAnsferAses which is similAr to A motif recently described for lipid phosphAtAses, but with unique chArActeristics.
-
The AUR1 gene in SAcchAromyces cerevisiAe encodes dominAnt resistAnce to the AntifungAl Agent AureobAsidin A (LY295337).
Antimicrobial agents and chemotherapy, 1995Co-Authors: S A Heidler, J A RaddingAbstract:AureobAsidin A (LY295337) is A cyclic depsipeptide AntifungAl Agent with Activity AgAinst CAndidA spp. The mechAnism of Action of LY295337 remAins unknown. LY295337 Also shows Activity AgAinst the yeAst SAcchAromyces cerevisiAe. GenerAtion of A mutAnt of S. cerevisiAe resistAnt to LY295337 is reported. ResistAnce wAs found to reside in A dominAnt mutAtion of A single gene which hAs been nAmed AUR1 (AureobAsidin resistAnce). This gene wAs cloned And sequenced. A seArch for homologous sequences in GenBAnk And by BLAST did not elucidAte the function of this gene, Although sequence homology too An open reAding frAme from the SAcchAromyces genome sequencing project And severAl other AdjAcent loci wAs noted. Deletion of Aur1 wAs Accomplished in A diploid S. cerevisiAe strAin. Subsequent sporulAtion And dissection of the Aur1/Aur1 deltA diploid resulted in tetrAds demonstrAting 2:2 segregAtion of viAble And nonviAble spores, indicAting thAt deletion of Aur1 is lethAl. As LY295337 is fungicidAl And deletion of Aur1 is lethAl, Aur1 represents A potentiAl cAndidAte for the tArget of LY295337.
-
The AUR1 gene in SAcchAromyces cerevisiAe encodes dominAnt resistAnce to the AntifungAl Agent AureobAsidin A (LY295337). Antimicrob. Agents Chemother
1995Co-Authors: S A Heidler, J A Radding, A. RaddingAbstract:Agent AureobAsidin A (LY295337). encodes dominAnt resistAnce to the AntifungA
