Molecule Information

General Information of the Molecule (ID: Mol01090)

• Name: Sterol 14-alpha demethylase cyp51A (CYP51A) ,Aspergillus niger
• Synonyms: ABL_04779
• Molecule Type: Protein
• Gene Name: ABL_04779
• Sequence:
  MAAIAPNPLNAPDTAVSGQSDCQHHWSLAWFDTLSKGSPSGLIRLRNHREQCLLPLLTVF
  ANHCSGWTDVAQCQGHEPTTTYSFDVLLLTFSFTNTFPINWSFFLPTVASRMAYLAVAGA
  YAFAALLVAIVLNVARQLLVRNEKEPPVVFHWIPFLGSTISYGMDPYAFFFSCRKKYGDI
  FTFVLLGKKTTVYLGVQGNDFILNGKLKDVSAEEVYSPLTTPVFGSDVVYDCPNSKLMEQ
  KKFIKFGLTQAALESHVQLIEKETLDYLRDSPRFNGASGVIDIPAAMAEITIYTAARALQ
  GEEVRKKLTAEFAELYHDLDKGFSPINFMLPWAPLPHNRKRDAAHARMREIYTDIINERR
  KNPDEEKSDMIWNLMHCTYKNGQPVPDKEIAHMMITLLMAGQHSSSSISSWIMLRLASEP
  QVLEELYQEQLTSLSNRNGVFEPLQYQDLDKLPLLQSVIKETLRIHSSIHSIMRKVKNPL
  PVPGTSYVIPEDRVLLASPGVTALSDEYFPNATRWDPHRWENQPDKEEEGEMVDYGYGSV
  SKGTASPYLPFGAGRHRCIGEKFAYVNLGVIIATIVRHLKLFNVDGRKGVPGTDYSTLFS
  GPLKPAIVGWERRIQDNSKGSLN
• Uniprot ID: A0A100IIZ2_ASPNG

Kingdom: Fungi
Phylum: Ascomycota
Class: Eurotiomycetes
Order: Eurotiales
Family: Aspergillaceae
Genus: Aspergillus
Species: Aspergillus niger

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Efinaconazole

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Tinea unguium [ICD-11: 1F28.1] [1]

• Sensitive Disease: Tinea unguium [ICD-11: 1F28.1]
• Sensitive Drug: Efinaconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Antifungal susceptibility assay
• Mechanism Description: The expression of?cyp51A?mRNA was induced by the addition of the azole antifungal drug efinaconazole, whereas no such induction was detected for?cyp51B, suggesting that Cyp51A functions as an azole-responsive Cyp51 isozyme. To explore the contribution of Cyp51A to susceptibility to azole drugs, the neomycin phosphotransferase (nptII) gene cassette was inserted into the?cyp51A?3'-untranslated region of deltaku80?to destabilize the mRNA of?cyp51A. In this mutant, the induction of?cyp51A?mRNA expression by efinaconazole was diminished. The minimum inhibitory concentration for several azole drugs of this strain was reduced, suggesting that dermatophyte Cyp51A contributes to the tolerance for azole drugs.

Posaconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Aspergillus niger infection [ICD-11: 1F20.3] [2]

• Resistant Disease: Aspergillus niger infection [ICD-11: 1F20.3]
• Resistant Drug: Posaconazole
• Molecule Alteration: Missense mutation; p.R228Q
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Aspergillus niger strain; 5061
• Experiment for Molecule Alteration: PCR amplification and sequence analysis
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Amino acid changes in ERG11 may contribute to Candida albicans emerging posaconazole resistance.

References

• Ref 1: An efficient gene targeting system using deltaku80 and functional analysis of Cyp51A in Trichophyton rubrum. AMB Express. 2024 Aug 31;14(1):96.
• Ref 2: Species Distribution and In Vitro Azole Susceptibility of Aspergillus Section Nigri Isolates from Clinical and Environmental Settings. J Clin Microbiol. 2016 Sep;54(9):2365-72. doi: 10.1128/JCM.01075-16. Epub 2016 Jul 13.