Molecule Information

General Information of the Molecule (ID: Mol00889)

• Name: D-glucan-1,3-beta--UDP glucosyltransferase (FKS1) ,Candida glabrata
• Synonyms: FKS2; AO440_003426; EC 2.4.1.34
• Molecule Type: Protein
• Gene Name: FKS2
• Sequence:
  MSYDQGGNGNWQNTDPNGNYYYNGAENNEFYDQDYASQQPEQQQGGEGYYDEYGQPNYNY
  MNDPQQGQMPQQQPGGYDNDGYYDSYYNNQMNAGVGNGLGPDQTNFSDFSSYGPPPFQNN
  QANYTPSQLSYSNNGMGSNGMNMSGSSTPVYGNYDPNAIAMTLPNDPYPAWTADPQSPVS
  IEQIEDVFIDLTNKFGFQRDSMRNIFDLFMTLLDSRTSRMSPDQALLSVHADYIGGDTAN
  YKKWYFAAQLDMDDEVGFRNMNLGKLSRKARKAKKKNKKAMEEANPEDAAEVLNKIEGDN
  SLEASDFRWKTKMNMLTPIERVRQVALYMLIWGEANQVRFTSECLCFIYKCASDYLESPL
  CQQRTEPIPEGDYLNRVITPIYQFIRNQVYEIVDGRYVKREKDHNKIIGYDDVNQLFWYP
  EGITKIVLEDGTKLTDIPSEERYLRLGEVAWNDVFFKTYKETRTWLHLVTNFNRIWIMHV
  SVYWMYVAYNSPTFYTHNYQQLVNNQPVPAYRWASAALAGTVASAIQLFATVCEWWFVPR
  KWAGAQHLSRRFWFLCGILGVNLGPLIFVFAYEKDTVQSKAGHAVAAVTFFIAVATVLFF
  SIMPLGGLFTSYMQKSSRRYVASQTFTASFAPLQGLDRWLSYLVWVTVFAAKYSESYFFL
  ILSLRDPIRILSTTTMRCTGEYWWGSKLCRHQSKIVLGFMIATDFILFFLDTYLWYIVVN
  TVFSVGKSFYLGISILTPWRNIFTRLPKRIYSKILATTDMEIKYKPKVLISQIWNAIIIS
  MYREHLLAIDHVQKLLYHQVPSEIEGKRTLRAPTFFVSQDDNNFETEFFPRNSEAERRIS
  FFAQSLATPMPEPLPVDNMPTFTVLTPHYSERILLSLREIIREDDQFSRVTLLEYLKQLH
  PVEWECFVKDTKILAEETAAYENEEPQDPEKSDALKTQIDDLPFYCIGFKSAAPEYTLRT
  RIWASLRSQTLYRTVSGFMNYARAIKLLYRVENPEIVQMFGGNAEGLERELEKMARRKFK
  FLVSMQRLAKFKPHELENTEFLLRAYPDLQIAYLDEEPPLNEGEEPRIYSALIDGHCEML
  ENGRRRPKFRVQLSGNPILGDGKSDNQNHALIFYRGEYIQLIDANQDNYLEECLKIRSVL
  AEFEELNAEPVYPYTPGVKYEDQKTNHPVAIVGAREYIFSENSGVLGDVAAGKEQTFGTL
  FARTLAQIGGKLHYGHPDFINATFMTTRSGLSKAQKGLHLNEDIYAGMNALLRGGRIKHC
  EYYQCGKGRDLGFGTILNFTTKIGAGMGEQMLSREYYYLGTQLPVDRFLTFYYAHPGFHL
  NNLFIQLSLQMFMLTLVNLHALAHESILCIYDRNKPKTDVLYPIGCYNFSPAIDWIRRYT
  LSIFIVFWIAFVPIVVQELIERGLWKATQRFFRHILSLSPMFEVFAGQIYSAALLSDMTV
  GGARYISTGRGFATSRIPFSILYSRFASSAIYMGARSMLMLLFGTVAHWQAPLLWFWASL
  SALLFSPFIFNPHQFSWEDFFLDYRDYIRWLSRGNNKYHKNSWIGYVRMARSRITGFKRK
  LIGDDSEKAAGDANRAHRTNLILAELIPTAINAGSCFIGFTFINAQTGVKATDDDRVNSV
  LRVVLCTLGPIAVDVGVLFFCLGMSCCSGPLFGMCCKKTGAVMAAVAHGVSVVIHIGFFI
  VMWVLEGFNFTRMLVGVATVIQCQRFIFQLMTILLLTREFKNDHANTAFWTGKWYGSGFG
  YMAWTQPMRELTAKVIEMSEFAADFVLGHVILFAQFPVLCIPAIDKFHSIMLFWLKPSRH
  IRPPIYSLKQSRLRKRMVKRYLTLYIIIFLVFAGAIVGPAVAASHVPQDIGHTLTGPFHN
  IVQPRNKSNNDTGLQISTYSNHYYTHTPSLKTWSTIK
• Uniprot ID: F5BCZ9_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.F659V (c.T1975G)
• 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.F659S(c.T1976C)
• 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: Frameshift mutation; p.F659del(c.1974-CTT-1976)
• 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: Nonsense mutation; p.R1377STOP (c.A4129T)
• 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.F659V (c.T1975G)
• 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.F659S (c.T1976C)
• 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.F659del (c.1974-CTT-1976)
• 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: Nonsense mutation; p.R1377STOP (c.A4129T)
• 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.F659V (c.T1975G)
• 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.F659S (c.T1976C)
• 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: Frameshift mutation; p.F659del (c.1974-CTT-1976)
• 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: Nonsense mutation; p.R1377STOP (c.A4129T)
• 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.