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NSG2 (ORF19.273) Encoding Protein Controls Sensitivity of Candida albicans to Azoles through Regulating the Synthesis of C14-Methylated Sterols
- Source :
- Frontiers in Microbiology, Frontiers in Microbiology, Vol 9 (2018)
- Publication Year :
- 2018
- Publisher :
- Frontiers Media S.A., 2018.
-
Abstract
- Antifungal azole drugs inhibit the synthesis of ergosterol and cause the accumulation of sterols containing a 14α-methyl group, which is related to the properties of cell membrane. Due to the frequent recurrence of fungal infections and clinical long-term prophylaxis, azole resistance is increasing rapidly. In our research, Nsg2p, encoded by the ORF19.273 in Candida albicans, is found to be involved in the inhibition of 14α-methylated sterols and resistance to azoles. Under the action of fluconazole, nsg2Δ/Δ mutants are seriously damaged in the integrity and functions of cell membranes with a decrease of ergosterol ratio and an increase of both obtusifoliol and 14α-methylfecosterol ratio. The balance between ergosterol and 14α-methyl sterols mediated by NSG2 plays an important role in C. albicans responding to azoles in vitro as well as in vivo. These phenotypes are completely different from those of Nsg2p in Saccharomyces cerevisiae, which is proved to increase the stability of HMG-CoA and resistance to lovastatin. Based on the evidence above, it is indicated that the decrease of 14α-methylated sterols is an azole-resistant mechanism in C. albicans, which may provide new strategies for overcoming the problems of azole resistance.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
azoles
030106 microbiology
lcsh:QR1-502
Drug resistance
sterols
Microbiology
lcsh:Microbiology
Cell membrane
03 medical and health sciences
chemistry.chemical_compound
In vivo
Candida albicans
medicine
polycyclic compounds
Original Research
chemistry.chemical_classification
Ergosterol
drug resistance
biology
biology.organism_classification
Corpus albicans
NSG2
030104 developmental biology
medicine.anatomical_structure
chemistry
Biochemistry
Azole
lipids (amino acids, peptides, and proteins)
Fluconazole
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 1664302X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Microbiology
- Accession number :
- edsair.doi.dedup.....6a06739eac69ebe747a9193e9066e06a