Molecule Information

General Information of the Molecule (ID: Mol00890)

• Name: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) ,Candida glabrata
• Synonyms: FKS1; fks1; AO440_001525; EC 2.4.1.34
• Molecule Type: Protein
• Gene Name: FKS1
• Gene ID: 2888318
• Sequence:
  MSYNNNGQQMSDQGYYDNNQGYYQPEDQQNGQAMYGDEGYYDPNISGGDYYNQPPPPPNM
  MGQDMENFSDFSSYGPPGVQGYDYQNMNQSGQYTPSQMSYNGDPNSGSSTPIYGNGMSAY
  DPNAIAMALPNDPYPAWTADSQSPVPIEQIEDVFIDLTNKFGFQRDSMRNMFDHFMTLLD
  SRTSRMAPDQALLSLHADYIGGDTANYKKWYFAAQLDMDDEVGFRNMSLGKLSRKARKAK
  KKNKKAMEEANPEDAEDILNKLEGDNSLEAADFRWKTKMNALTPIERVRQIALYLLIWGE
  ANQVRFTSECLCFIYKCATDYLNSPLCQQRTEPMPEGDYLNRVITPLYRFIRNQVYEIVD
  GRYVKREKDHHKVIGYDDVNQLFWYPEGIAKIVFEDSTKLIEIPAEERYLRLGEVSWDDV
  FFKTYKETRSWFHMITNFNRIWIMHVTIFWMYVAYNSPTFYTHNYQQLVNNQPPAAYKWA
  SAALGGTVASFIQLLATICEWSFVPRKWAGAQHLSRRFWFLCLIFAVNLGPIIFVFAYEK
  DTVQSKAGHAVAAVMFFVAVATLLFFSVMPLGGLFTSYMQKSTRRYVASQTFTASFAPLH
  GLDRWLSYLVWVTVFAAKYAESYYFLILSLRDPIRILSTTTMRCTGEYWWGSKLCRHQSK
  IVLGLMIATDFILFFLDTYLWYIVVNTVFSVGKSFYLGISILTPWRNIFTRLPKRIYSKI
  LATTDMEIKYKPKVLISQVWNAIIISMYREHLLAIDHVQKLLYHQVPSEIEGKRTLRAPT
  FFVSQDDNNFETEFFPRNSEAERRISFFAQSLATPMPEPLPVDNMPTFTVLTPHYAERIL
  LSLREIIREDDQFSRVTLLEYLKQLHPVEWECFVKDTKILAEETAAYEGMDDQDPEKEDA
  LKNQIDDLPFYCIGFKSAAPEYTLRTRIWASLRSQTLYRTVSGFMNYARAIKLLYRVENP
  EIVQMFGGNAEGLERELEKMARRKFKFLVSMQRLAKFKPHELENAEFLLRAYPDLQIAYL
  DEEPPLNEGEEPRIYSALIDGHCEILENGRRRPKFRVQLSGNPILGDGKSDNQNHALIFY
  RGEYIQLIDANQDNYLEECLKIRSVLAEFEELNAEQVYPYSPGVKYEDQNTNHPVAIVGA
  REYIFSENSGVLGDVAAGKEQTFGTLFARTLAQIGGKLHYGHPDFINATFMTTRGGISKA
  QKGLHLNEDIYAGMNALLRGGRIKHCEYYQCGKGRDLGFGTILNFTTKIGAGMGEQMLSR
  EYYYLGTQLPIDRFLTFYYAHPGFHLNNLFIQLSLQMFMLTLVNLHALAHESIICIYDKN
  KPKTDVLYPIGCYNFSPAIDWVRRYTLSIFIVFWIAFVPIVVQELIERGLWKATQRFFRH
  ILSLSPMFEVFAGQIYSSALLSDLTVGGARYISTGRGFATSRIPFSILYSRFAGSAIYMG
  ARSMLMLLFGTVAHWQAPLLWFWASLSALLFSPFIFNPHQFSWEDFFLDYRDYIRWLSRG
  NSKYHRNSWIGYVRMARSRITGFKRKLVGDESEKAAGDASRAHRTNLILAEIIPNAIYAA
  GCFVGFTFINAQTGVKTTDDDRVNSVLRIIICTLAPIVIDIGVLFFVLGMSCCSGPLFGM
  CCKRTGSVMAGFAHGIAVIVHIGFFIVMWVLEGFNFTRMLLGVVTMIQCQRLIFQCMTVL
  MLTREFKNDHANTAFWTGKWYGSGFGYMAWTQPTRELTAKVIELSEFAADFVLGHVILFA
  QFPVLCIPAIDKFHSIMLFWLKPSRQIRPPIYSLKQSRLRKRMVKRYLTLYIIVFLVFAG
  CIVGPAVASSHVAKDLGHQLTGTFHNLVQPRNVSNNDTGFGISTYSNHYYTHTPSLKTWS
  TIK
• Uniprot ID: E2GKZ4_CANGB

Kingdom: Fungi
Phylum: Ascomycota
Class: Saccharomycetes
Order: Saccharomycetales
Family: Saccharomycetaceae
Genus: Nakaseomyces
Species: Candida glabrata

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Anidulafungin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Anidulafungin
• Molecule Alteration: Missense mutation; p.D632G (c.A1895G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Anidulafungin
• Molecule Alteration: Missense mutation; p.D632E (c.T1896G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Recently, three reports showed that amino acid substitutions in Fks1p (D632E) and Fks2p (F659V) are responsible for clinical echinocandin resistance in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Anidulafungin
• Molecule Alteration: Missense mutation; p.D632Y (c.G1894T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Anidulafungin
• Molecule Alteration: Missense mutation; p.F625S (c.T1874C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Anidulafungin
• Molecule Alteration: Missense mutation; p.S629P (c.T1885C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Caspofungin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.D632G (c.A1895G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.D632E (c.T1896G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Recently, three reports showed that amino acid substitutions in Fks1p (D632E) and Fks2p (F659V) are responsible for clinical echinocandin resistance in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.D632Y (c.G1894T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.F625S (c.T1874C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Caspofungin
• Molecule Alteration: Missense mutation; p.S629P (c.T1885C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Micafungin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Micafungin
• Molecule Alteration: Missense mutation; p.D632G (c.A1895G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Micafungin
• Molecule Alteration: Missense mutation; p.D632E (c.T1896G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Recently, three reports showed that amino acid substitutions in Fks1p (D632E) and Fks2p (F659V) are responsible for clinical echinocandin resistance in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Micafungin
• Molecule Alteration: Missense mutation; p.D632Y (c.G1894T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Micafungin
• Molecule Alteration: Missense mutation; p.F625S (c.T1874C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

Disease Class: Candida glabrata infection [1]

• Resistant Disease: Candida glabrata infection [ICD-11: 1F23.3]
• Resistant Drug: Micafungin
• Molecule Alteration: Missense mutation; p.S629P (c.T1885C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida glabrata strain; 5478
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: Fks1p and Fks2p amino acid substitutions confer reduced echinocandin susceptibility in C. glabrata.

References

• Ref 1: Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-beta-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother. 2009 Sep;53(9):3690-9. doi: 10.1128/AAC.00443-09. Epub 2009 Jun 22.