Related Experiment Videos
Resistance of Candida parapsilosis to drugs
Abstract:
Several strains of Candida parapsilosis, isolated independently in our laboratory, had their resistance compared to a series of inhibitors which act either at the level of mitochondrial ribosomes (chloramphenicol, erythromycin, paromomycin) or at the level of mitochondrial respiration and oxidative phosphorylation (oligomycin, antimycin A, diuron, carbonylcyanide m-chlorophenylhydrazone). Cells were grown on glycerol media supplemented with one of these inhibitors, and it was demonstrated that the resistance of these yeasts to a large spectrum of antibiotics was due to several features: a resistance to oligomycin was found at the permeation level; the resistance to the other drugs was correlated to the relative insensitivity of cytochrome biosynthesis to the drugs; the cells developed, at the same time, two types of alternative pathways: the one branched at the ubiquinone level which drove electrons from Krebs cycle substrates to oxygen, and the other, antimycin A-insensitive but inhibited by amytal, salicylhydroxamic acid and high cyanide concentrations. This secondary mitochondrial pathway, driving reducing equivalents from cytoplasmic NADH to cytochrome c and then to cytochrome aa3 or to alternate oxidase, allowed the growth of Candida parapsilosis on a non fermentescible medium, supplemented with these drugs.
Insights
Candida parapsilosis exhibits resistance to mitochondrial inhibitors through permeation changes and alternative respiratory pathways. These adaptations allow yeast growth in the presence of various antibiotics, highlighting unique survival mechanisms.
Area of Science:
- Mycology
- Molecular Biology
- Biochemistry
Background:
- Candida parapsilosis is an opportunistic fungal pathogen.
- Understanding its resistance mechanisms to antifungal agents is crucial for clinical management.
- Mitochondrial function is a key target for many antifungal drugs.
Purpose of the Study:
- To investigate the resistance mechanisms of Candida parapsilosis to mitochondrial inhibitors.
- To characterize the role of alternative respiratory pathways in drug resistance.
- To compare the efficacy of various inhibitors targeting mitochondrial ribosomes and respiration.
Main Methods:
- Yeast strains were grown on glycerol media with specific mitochondrial inhibitors.
- Resistance levels to chloramphenicol, erythromycin, paromomycin, oligomycin, antimycin A, diuron, and carbonylcyanide m-chlorophenylhydrazone were assessed.
- Analysis of cytochrome biosynthesis and development of alternative mitochondrial pathways.
Main Results:
- Resistance to oligomycin was observed at the permeation level.
- Resistance to other drugs correlated with insensitivity of cytochrome biosynthesis.
- Two alternative mitochondrial pathways were identified: one branching at ubiquinone and another antimycin A-insensitive pathway.
- These pathways enabled growth on non-fermentable media supplemented with inhibitors.
Conclusions:
- Candida parapsilosis employs multiple strategies to resist mitochondrial inhibitors.
- Permeation resistance and alternative respiratory pathways are key survival mechanisms.
- These findings provide insights into antifungal drug resistance in Candida species.