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Filamentation protects Candida albicans fromamphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1

View Article: PubMed Central - PubMed

ABSTRACT

The budding yeast Candida albicans is one of the mostsignificant fungal pathogens worldwide. It proliferates in two distinct celltypes: blastopores and filaments. Only cells that are able to transform from onecell type into the other are virulent in mouse disease models. Programmed celldeath is a controlled form of cell suicide that occurs when C.albicans cells are exposed to fungicidal drugs like amphotericin Band caspofungin, and to other stressful conditions. We now provide evidence thatsuggests that programmed cell death is cell-type specific in yeast: FilamentousC. albicans cells are more resistant to amphotericin B- andcaspofungin-induced programmed cell death than their blastospore counterparts.Finally, our genetic data suggests that this phenomenon is mediated by aprotective mechanism involving the yeast metacaspase, MCA1.

No MeSH data available.


Related in: MedlinePlus

FIGURE 1: Filamentous C. albicans cells are moreresistant than blastospores to AMB-induced programmed cell death. Exposure to amphotericin B leads to the generation of reactive oxygenspecies (ROS) and to caspase activation in C. albicanscells. Representative confocal scanning laser fluorescence images ofwild-type SC5314 C. albicans cells treated with 8 μg/ml AMBfor 3 hours in YPD. Staining with dihydrorhodamine 123 (DHR123) confirms thepresence of ROS (A) and with the FLICA assay for activation ofintracellular caspases (B). Error bars indicate standarddeviations for trials with at least three independent cultures, where atleast 300 cells were counted for each trial. No FLICA positive cells wereobserved in the no drug controls. A single asterisk indicates statisticalsignificance (p < 0.05) as compared to treated controls. Statisticalsignificance was determined with the unpaired Student’s t-test. Scale bar:50 μm. Viability curves compare survival of the following cells exposed toAMB: (C) wild type blastospores and wild type filaments inducedusing 10% FBS; (D) wild type blastospores and wild typefilaments induced using 0.5 g/l GlcNAc; (E)ΔΔefg1/efg1cph1/cph1 cells in YPD and ΔΔefg1/efg1cph1/cph1 cells following filamentous induction in YPD + 10%FBS, and (F)ΔΔflo8/flo8 cells in YPD andΔΔflo8/flo8 cells following filamentous induction inYPD + 10% FBS. Note that after 3 hr, cells cultured in rich media withoutany drugs were able to grow and to divide, hence the relative viabilitylevels that are greater than 100%. Error bars indicate standard deviationsfor trials with at least three independent cultures. A single, double, andtriple asterisk indicates a significance of p < 0.05, p < 0.005, and p< 0.0005, respectively, as compared to treated controls. Statisticalsignificance was determined with the unpaired Student’s t-test.
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Fig1: FIGURE 1: Filamentous C. albicans cells are moreresistant than blastospores to AMB-induced programmed cell death. Exposure to amphotericin B leads to the generation of reactive oxygenspecies (ROS) and to caspase activation in C. albicanscells. Representative confocal scanning laser fluorescence images ofwild-type SC5314 C. albicans cells treated with 8 μg/ml AMBfor 3 hours in YPD. Staining with dihydrorhodamine 123 (DHR123) confirms thepresence of ROS (A) and with the FLICA assay for activation ofintracellular caspases (B). Error bars indicate standarddeviations for trials with at least three independent cultures, where atleast 300 cells were counted for each trial. No FLICA positive cells wereobserved in the no drug controls. A single asterisk indicates statisticalsignificance (p < 0.05) as compared to treated controls. Statisticalsignificance was determined with the unpaired Student’s t-test. Scale bar:50 μm. Viability curves compare survival of the following cells exposed toAMB: (C) wild type blastospores and wild type filaments inducedusing 10% FBS; (D) wild type blastospores and wild typefilaments induced using 0.5 g/l GlcNAc; (E)ΔΔefg1/efg1cph1/cph1 cells in YPD and ΔΔefg1/efg1cph1/cph1 cells following filamentous induction in YPD + 10%FBS, and (F)ΔΔflo8/flo8 cells in YPD andΔΔflo8/flo8 cells following filamentous induction inYPD + 10% FBS. Note that after 3 hr, cells cultured in rich media withoutany drugs were able to grow and to divide, hence the relative viabilitylevels that are greater than 100%. Error bars indicate standard deviationsfor trials with at least three independent cultures. A single, double, andtriple asterisk indicates a significance of p < 0.05, p < 0.005, and p< 0.0005, respectively, as compared to treated controls. Statisticalsignificance was determined with the unpaired Student’s t-test.


Filamentation protects Candida albicans fromamphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1
FIGURE 1: Filamentous C. albicans cells are moreresistant than blastospores to AMB-induced programmed cell death. Exposure to amphotericin B leads to the generation of reactive oxygenspecies (ROS) and to caspase activation in C. albicanscells. Representative confocal scanning laser fluorescence images ofwild-type SC5314 C. albicans cells treated with 8 μg/ml AMBfor 3 hours in YPD. Staining with dihydrorhodamine 123 (DHR123) confirms thepresence of ROS (A) and with the FLICA assay for activation ofintracellular caspases (B). Error bars indicate standarddeviations for trials with at least three independent cultures, where atleast 300 cells were counted for each trial. No FLICA positive cells wereobserved in the no drug controls. A single asterisk indicates statisticalsignificance (p < 0.05) as compared to treated controls. Statisticalsignificance was determined with the unpaired Student’s t-test. Scale bar:50 μm. Viability curves compare survival of the following cells exposed toAMB: (C) wild type blastospores and wild type filaments inducedusing 10% FBS; (D) wild type blastospores and wild typefilaments induced using 0.5 g/l GlcNAc; (E)ΔΔefg1/efg1cph1/cph1 cells in YPD and ΔΔefg1/efg1cph1/cph1 cells following filamentous induction in YPD + 10%FBS, and (F)ΔΔflo8/flo8 cells in YPD andΔΔflo8/flo8 cells following filamentous induction inYPD + 10% FBS. Note that after 3 hr, cells cultured in rich media withoutany drugs were able to grow and to divide, hence the relative viabilitylevels that are greater than 100%. Error bars indicate standard deviationsfor trials with at least three independent cultures. A single, double, andtriple asterisk indicates a significance of p < 0.05, p < 0.005, and p< 0.0005, respectively, as compared to treated controls. Statisticalsignificance was determined with the unpaired Student’s t-test.
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Fig1: FIGURE 1: Filamentous C. albicans cells are moreresistant than blastospores to AMB-induced programmed cell death. Exposure to amphotericin B leads to the generation of reactive oxygenspecies (ROS) and to caspase activation in C. albicanscells. Representative confocal scanning laser fluorescence images ofwild-type SC5314 C. albicans cells treated with 8 μg/ml AMBfor 3 hours in YPD. Staining with dihydrorhodamine 123 (DHR123) confirms thepresence of ROS (A) and with the FLICA assay for activation ofintracellular caspases (B). Error bars indicate standarddeviations for trials with at least three independent cultures, where atleast 300 cells were counted for each trial. No FLICA positive cells wereobserved in the no drug controls. A single asterisk indicates statisticalsignificance (p < 0.05) as compared to treated controls. Statisticalsignificance was determined with the unpaired Student’s t-test. Scale bar:50 μm. Viability curves compare survival of the following cells exposed toAMB: (C) wild type blastospores and wild type filaments inducedusing 10% FBS; (D) wild type blastospores and wild typefilaments induced using 0.5 g/l GlcNAc; (E)ΔΔefg1/efg1cph1/cph1 cells in YPD and ΔΔefg1/efg1cph1/cph1 cells following filamentous induction in YPD + 10%FBS, and (F)ΔΔflo8/flo8 cells in YPD andΔΔflo8/flo8 cells following filamentous induction inYPD + 10% FBS. Note that after 3 hr, cells cultured in rich media withoutany drugs were able to grow and to divide, hence the relative viabilitylevels that are greater than 100%. Error bars indicate standard deviationsfor trials with at least three independent cultures. A single, double, andtriple asterisk indicates a significance of p < 0.05, p < 0.005, and p< 0.0005, respectively, as compared to treated controls. Statisticalsignificance was determined with the unpaired Student’s t-test.

View Article: PubMed Central - PubMed

ABSTRACT

The budding yeast Candida albicans is one of the mostsignificant fungal pathogens worldwide. It proliferates in two distinct celltypes: blastopores and filaments. Only cells that are able to transform from onecell type into the other are virulent in mouse disease models. Programmed celldeath is a controlled form of cell suicide that occurs when C.albicans cells are exposed to fungicidal drugs like amphotericin Band caspofungin, and to other stressful conditions. We now provide evidence thatsuggests that programmed cell death is cell-type specific in yeast: FilamentousC. albicans cells are more resistant to amphotericin B- andcaspofungin-induced programmed cell death than their blastospore counterparts.Finally, our genetic data suggests that this phenomenon is mediated by aprotective mechanism involving the yeast metacaspase, MCA1.

No MeSH data available.


Related in: MedlinePlus