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Impact of Farnesol as a Modulator of Efflux Pumps in a Fluconazole-Resistant Strain of Candida albicans
L. Černáková, S. Dižová, D. Gášková, I. Jančíková, H. Bujdáková,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
PubMed
30785845
DOI
10.1089/mdr.2017.0332
Knihovny.cz E-zdroje
- MeSH
- ABC transportéry metabolismus MeSH
- antifungální látky farmakologie MeSH
- biologický transport účinky léků MeSH
- Candida albicans účinky léků metabolismus MeSH
- farnesol farmakologie MeSH
- flukonazol farmakologie MeSH
- fungální léková rezistence účinky léků MeSH
- fungální proteiny metabolismus MeSH
- membránové transportní proteiny metabolismus MeSH
- mikrobiální testy citlivosti metody MeSH
- Publikační typ
- časopisecké články MeSH
Aim: This work studied the impact of the quorum-sensing molecule, farnesol (FAR), on fluconazole (FLC)-resistant Candida albicans isolate CY 1123 compared with the susceptible standard strain C. albicans SC5314. The genes encoding efflux pumps belonging to the ATP-binding cassette (ABC) and major facilitator superfamilies, together with overexpression or point mutation of the ERG11 gene, are the main resistance mechanisms to azole antifungal drugs. Results: The upregulation of genes coding for CDR1, CDR2, and MDR1 were confirmed by qPCR with respect to the housekeeping gene ACT1 in the resistant strain. The contribution of the ERG11 gene was also observed. Markedly, increased pump activity (Cdr1 and/or Cdr2) in the CY 1123 strain was confirmed using diS-C3(3) assay. However, the addition of FAR to the yeasts diminished the difference in staining levels between the SC5314 and CY 1123 strains, demonstrating the concentration-dependent character that could be caused by an effective modulation of Cdr pumps. FAR (60 and 100 μM) was also able to decrease the minimal inhibitory concentrations (MIC50), denoting the inhibition of planktonic cells by 50%, from 8 to 4 μg/mL of FLC when the resistant strain CY 1123 was not cultivated with FLC. However, when it was exposed to 64 μg/mL of FLC, the MIC50 shifted from 64 to 8 μg/mL. Conclusion: Besides the many other effects of FAR on eukaryotic and prokaryotic cells, it also affects ABC efflux transporters, resulting in changes in resistance to azoles in C. albicans isolates. However, this effect is dependent on FAR concentrations.
Citace poskytuje Crossref.org
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