Molecule Information

General Information of the Molecule (ID: Mol01015)

• Name: Multidrug resistance protein CDR2 (CDR2) ,Candida albicans
• Synonyms: CAALFM_C304890WA; CaO19.13379; CaO19.5958
• Molecule Type: Protein
• Gene Name: CDR2
• Gene ID: 3635265
• Sequence:
  MSTANTSLSQQLDEKPWVDASDNSSVQEYQGFDATASHNIQDLARKLTHGSTNGDHHSAN
  DLARYLSHMSDIPGVSPFNGNISHEQLDPDSENFNAKYWVKNLKKLFESDSDYYKPSKLG
  VAYRNLRAYGIANDSDYQPTVTNALWKFTTEAINKLKKPDDSKYFDILKSMDAIMRPGEL
  TVVLGRPGAGCSTLLKTIAVNTYGFHIGKESQITYDGLSPHDIERHYRGDVIYSAETDVH
  FPHLSVGDTLEFAARLRTPQNRGEGIDRETYAKHMASVYMATYGLSHTRNTNVGNDFVRG
  VSGGERKRVSIAEASLSGANIQCWDNATRGLDSATALEFIRALKTSATILDTTPLIAIYQ
  CSQDAYELFDNVVVLYEGYQIFFGKASKAKEYFENMGWKCPQRQTTADFLTSLTNPAERE
  PLPGYEDKVPRTAQEFETFWKNSPEYAELTKEIDEYFVECERSNTGETYRESHVAKQSNN
  TRPSSPYTVSFFMQVRYVIARNFLRMKGDPSIPLISILSQLVMGLILASVFFNLRKSTDT
  FYFRGGALFFSVLFNAFSSLLEILSLYEARPIVEKHRKYALYRPSADALASIISELPVKL
  LMTMSFNIVYYFMVNLRRTAGNFFFYWLMCASCTLVMSHMFRSIGAVTTTIATAMSLSTV
  FLLAMIIYAGFVLPIPYILGWSRWIRYINPVTYIFESLMVNEFHGREFECGQYIPSGPGF
  ENLPVENKVCTTVGSTPGSTVVQGTEYIKLAYQFYSSHKWRNFGITVAFAVFFLGVYVAL
  TEFNKGAMQKGEIVLFLKGSLKKHKRKTAASNKGDIEAGPVAGKLDYQDEAEAVNNEKFT
  EKGSTGSVDFPENREIFFWRDLTYQVKIKKEDRVILDHVDGWVKPGQITALMGASGAGKT
  TLLNCLSERVTTGIITDGERLVNGHALDSSFQRSIGYVQQQDVHLETTTVREALQFSAYL
  RQSNKISKKEKDDYVDYVIDLLEMTDYADALVGVAGEGLNVEQRKRLTIGVELVAKPKLL
  LFLDEPTSGLDSQTAWSICKLMRKLADHGQAILCTIHQPSALIMAEFDKLLFLQKGGRTA
  YFGELGENCQTMINYFEKYGADPCPKEANPAEWMLQVVGAAPGSHAKQDYFEVWRNSSEY
  QAVREEINRMEAELSKLPRDNDPEALLKYAAPLWKQYLLVSWRTIVQDWRSPGYIYSKLI
  LVISSSLFIGFSFFKSKNNLQGLQSQMLAVFMFFVPFTTFIDQMLPYFVKHRAVYEVREA
  PSRTFSWFAFIAGQITSEIPFQIVVGTISYFCWYYPVGLYANAEPTDSVNSRGVLMWMLL
  TAFYVYTSTMGQLAISLNELIDNAANLATTLFTLCLMFCGVLAGPNVIPGFWIFMYRCNP
  FTYLIQAILSTGLANAKVTCAPRELVTLKPPMGETCSSFIGPYTEAAGGYFSTNSDGTCS
  VCRIDSTNQFLESINALFSQRWRNFGIFVAFIGINIILTIFFYWLARVPKGNREKKMKK
• Function: Multidrug efflux transporter. Confers resistance to azole antifungal agents, to other antifungals (terbinafine, amorolfine) and to a variety of metabolic inhibitors.
• Uniprot ID: CDR2_CANAL

Kingdom: Fungi
Phylum: Ascomycota
Class: Saccharomycetes
Order: Saccharomycetales
Family: Debaryomycetaceae
Genus: Candida
Species: Candida albicans

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Fluconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Candidosis [1]

• Resistant Disease: Candidosis [ICD-11: 1F23.0]
• Resistant Drug: Fluconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: South America Candida albicans strain; 5476
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Overexpression of the genes ERG11, CDR1, CDR2, MDR1, and FLU1 has been linked to fluconazole resistance (White et al., 1998) and was investigated as a mechanism of resistance in our clinical isolates by using real-time RT-PCR.

Disease Class: Mycotic vaginitis [2]

• Resistant Disease: Mycotic vaginitis [ICD-11: 1F2Y.0]
• Resistant Drug: Fluconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida albicans strain; 5476
• Experiment for Molecule Alteration: Northern blot analysis
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Resistance mechanisms that have been identified include overexpression of the MDR1 gene encoding a drug efflux pump, increased expression of the CDR1 and CDR2 genes, overexpression of the ERG11 gene coding for the FLU target enzyme, and alterations in the structure of Erg11p.

Disease Class: Recurrent oropharyngeal candidiasis [3], [4], [5]

• Resistant Disease: Recurrent oropharyngeal candidiasis [ICD-11: 1F23.6]
• Resistant Drug: Fluconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida albicans strain; 5476
• Experiment for Molecule Alteration: Northern blotting analysis
• Experiment for Drug Resistance: NCCLS method M-27A with broth macrodilution techniques assay
• Mechanism Description: The genes coding for several ABC transporters in C. albicans have been identified, including several CDR genes (19, 26). CDR1 and CDR2 were the first two members of this family identified in C. albicans, and both CDR1 and CDR2 have been described as playing a role in fluconazole resistance.

Disease Class: Recurrent oropharyngeal candidiasis [6]

• Resistant Disease: Recurrent oropharyngeal candidiasis [ICD-11: 1F23.6]
• Resistant Drug: Fluconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Candida albicans strain; 5476
• Mechanism Description: In C. albicans, overexpression of two homologous ABC transporters, Cdr1 and Cdr2, have been frequently implicated in azole resistance, particularly in patients receiving long-term antifungal therapy.

References

• Ref 1: Evaluation of fluconazole resistance mechanisms in candida albicans clinical isolates from HIV-infected patients in Brazil. Diagn Microbiol Infect Dis. 2004 Sep;50(1):25-32. doi: 10.1016/j.diagmicrobio.2004.04.009.
• Ref 2: Resistance mechanisms in fluconazole-resistant Candida albicans isolates from vaginal candidiasis. Int J Antimicrob Agents. 2006 May;27(5):403-8. doi: 10.1016/j.ijantimicag.2005.12.005. Epub 2006 Apr 18.
• Ref 3: Multiple resistant phenotypes of Candida albicans coexist during episodes of oropharyngeal candidiasis in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1999 Jul;43(7):1621-30. doi: 10.1128/AAC.43.7.1621.
• Ref 4: Application of real-time quantitative PCR to molecular analysis of Candida albicans strains exhibiting reduced susceptibility to azoles. Antimicrob Agents Chemother. 2004 Jun;48(6):2124-31. doi: 10.1128/AAC.48.6.2124-2131.2004.
• Ref 5: Distinct patterns of gene expression associated with development of fluconazole resistance in serial candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrob Agents Chemother. 1998 Nov;42(11):2932-7. doi: 10.1128/AAC.42.11.2932.
• Ref 6: Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond .Chem Rev. 2021 Mar 24;121(6):3390-3411. doi: 10.1021/acs.chemrev.0c00199. Epub 2020 May 22. 10.1021/acs.chemrev.0c00199