Molecule Information

General Information of the Molecule (ID: Mol00767)

• Name: ABC transporter (ABCT) ,Cryptococcus neoformans
• Synonyms: AFR1; ABC-transporter
• Molecule Type: Protein
• Gene Name: AFR1
• Sequence:
  MSATGVPAELNNLGAPITATTQNPSGLANSQVTSGPASSATQHDEHRSSAGNTLADEEND
  KAVESEKAEVIDAAADGKQKRLAADSSENIVTELEPHHVSIHRGKEEFAALERRYSTLSQ
  QSQHELHRPTTRHSVRSSFSRKDRVVSRLTQDDAEKAKEGEGEFNLVDVLRSGRENQDEA
  GIKRKAVGVIWEDLEVIGAGGMRINIRNFSSAIIEQFMMPAFKILSIFGVNPFAPKPKAI
  LHPSSGLLKPGEMCLVLGRPGAGCTTFLKTITNQRAGFMEIKGNVEYAGVGWKEMRKRYG
  GEVVYNQEDDDHLPTLTVAQTIRFAPATKTPKKKIPGVSAKQFQDDMLDLLLSMLNIKHT
  ANTIVGNAYVRGVSGGERKRVSIAEMFCSGATVCSWDNSTRGLDASTALDYAKSLRLLTD
  IMGQTTFVSLYQAGEGIYDQFDKVLVLNEGHVAYFGPAKEARQYMIGLGYRDLPRQTTAD
  YLSGCTDVNERRFADGRDETNVPATPEEMDKAYKESEVCARMTREREEYKQLMAEDATAR
  EDFRQAVLEQKHKGVSKKSPYTVSFLQQVFIIFKRQLRLKFQDHFGISTGYATAIISALI
  VGSVYFRLPETASGAFTRGGLLFLGLLFNALTSFSELPSQMLGRSVLYRQNEYRFYRPAA
  FALAAVLADVPYNASVIFLFSIVLYFMGGLYSSGGAFFMFFLFVFLTFMVMSAFFRTLGV
  ATSDYNVAARLASVLISFMVTYTGYMIPVQRMKRWLFWIFYLNPLSYGYEAIFANEFSRI
  NLTCDSSYTIPRNIPEAGITGYPDTLGPNQMCSIFGSTPGDPNVSGSDYMATGYSYYKAH
  IWRNFGILLGFFAFFMFLQMLFIEVLEQGAKHFSINVYKKEDKDLKAKNERLAERLEAFR
  AGELEQDLSELKMRPEPFTWEVLNYTVPVPGGHRQLLNDIYGYVKPGSLTALMGASGAGK
  TTVLDVRASRKNIGVIEGDVLMNGRPIGTGFQRGCGYAEQQDTHEWTTTVREALRYSAYL
  RQPQHVPKQEKDDYVEDIIELLELQELADAMIGFPGYGLSVEARKRVTIGVELAAKPELL
  LFLDEPTSGLDGQSAYNIVRFLKKLCAAGQKILCTIHQPNALLFQSFDRLLLLQRGGECV
  YFGDIGPDSKVLIDYLERNGAKVPHDANPAEFMLEAIGAGSRKRIGSDWGEKWRNSPEFA
  EVKREIQELKAEALAKPVEEKSNRTEYATSFFFQLKTVLRRTNVALWRNADYQWTRLFAH
  LAIGLIVTLTFLQLDNSVQSLQYRVFAIFFATVLPALILAQIEPQYIMSRMTFNREASSK
  MYSSTVFALTQLLSEMPYSLGCAVSFFLLLYYGVGFPYASSRAGYFFLMILVTEVYAVTL
  GQAVAALSPTILIAALFNPFLLVLFSIFCGVTAPPPTLPYFWRKWMWPLDPFTRLISGLV
  STVLQDQEVVCKDGEYQVFPAPSGQTCQQWAGAFAEAIGGYINNPDSTGDCQFCQYRTGQ
  AFFTPLEISFSTRWRDFGIFICYVVFNILVLLIAARFLKWQRR
• Uniprot ID: Q8X0Z3_CRYNE

Kingdom: Fungi
Phylum: Basidiomycota
Class: Tremellomycetes
Order: Tremellales
Family: Cryptococcaceae
Genus: Cryptococcus
Species: Cryptococcus neoformans

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) 3 drug(s) in total

Fluconazole

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cryptococcal meningitis [1]

• Sensitive Disease: Cryptococcal meningitis [ICD-11: 1D01.0]
• Sensitive Drug: Fluconazole
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Cryptococcus neoformans stiain BPY22.17; 5207
• Experiment for Molecule Alteration: Southern hybridization analysis; Northern hybridization analysis
• Experiment for Drug Resistance: Rhodamine 6G accumulation assay; M27-A assay
• Mechanism Description: We found that the MIC to fluconazole in the knock-out mutant cnafr reduced 16-fold compared to the parent strain BPY22.17, but was nearly equal to that of the matched fluconazole-susceptible strain BPY22 (although was still somewhat less susceptible than strain BPY22).

Itraconazole

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cryptococcal meningitis [1]

• Sensitive Disease: Cryptococcal meningitis [ICD-11: 1D01.0]
• Sensitive Drug: Itraconazole
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Cryptococcus neoformans stiain BPY22.17; 5207
• Experiment for Molecule Alteration: Southern hybridization analysis; Northern hybridization analysis
• Experiment for Drug Resistance: Rhodamine 6G accumulation assay; M27-A assay
• Mechanism Description: Again, disruption of CnAFR1 gene resulted in an increased susceptibility to ketoconazole and itraconazole, suggesting that these antifungal azoles are substrates for CnAfr1p.

Ketoconazole

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cryptococcal meningitis [1]

• Sensitive Disease: Cryptococcal meningitis [ICD-11: 1D01.0]
• Sensitive Drug: Ketoconazole
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Cryptococcus neoformans stiain BPY22.17; 5207
• Experiment for Molecule Alteration: Southern hybridization analysis; Northern hybridization analysis
• Experiment for Drug Resistance: Rhodamine 6G accumulation assay; M27-A assay
• Mechanism Description: Again, disruption of CnAFR1 gene resulted in an increased susceptibility to ketoconazole and itraconazole, suggesting that these antifungal azoles are substrates for CnAfr1p.

References

• Ref 1: Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol Microbiol. 2003 Jan;47(2):357-71. doi: 10.1046/j.1365-2958.2003.03281.x.