Oxidative stress by antimicrobial peptide pleurocidin triggers apoptosis in Candida albicans

Cho, Jae-Yong; Lee, Dong Gun

doi:10.1016/j.biochi.2011.07.011

Cited by 65 publications

(59 citation statements)

References 38 publications

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“…Release of cyt c requires an increase in mitochondrial membrane permeability during apoptosis (28). Our results show that, as in mammalian and yeast cells, ROS formation, changes in ⌬⌿ m , and cyt c release also correlate with apoptosis in Mucorales (35,36). Authors have also reported ROS-induced apoptosis in Aspergillus nidulans, Fusarium oxysporum, and Candida albicans cells (37)(38)(39).…”

Section: Discussionsupporting

confidence: 58%

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

Shirazi

Kontoyiannis

2013

Eukaryot Cell

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The calcineurin pathway regulates antifungal drug resistance and the virulence of several major human-pathogenic fungi, including the recalcitrant Mucorales. We hypothesized that the fungistatic triazoles posaconazole (PCZ) and itraconazole (ICZ) become fungicidal in the setting of the calcineurin inhibitor tacrolimus (TCR) and that such an effect is mediated through apoptosis. Fungicidal activity and apoptosis were studied using standard microbiological techniques and hyphal metabolic and vital dye reduction assays at 37°C in RPMI 1640. Apoptosis was characterized by detecting intracellular Ca 2؉ , phosphatidylserine (PS) externalization, DNA fragmentation, plasma membrane integrity, chromatin condensation, reactive oxygen species (ROS) generation, caspase-like activity, ATP, and cytochrome c release. MICs for PCZ and ICZ alone were significantly higher (8 to 128 g/ml) than those of PCZ or ICZ plus TCR (0.25 to 4 g/ml) for Rhizopus oryzae, Cunninghamella bertholletiae, and Mucor circinelloides. Both PCZ and ICZ in combination with TCR became fungicidal, and their activity was mediated through increased apoptotic cell death of R. oryzae (10 to 50%), C. bertholletiae (5 to 50%), and M. circinelloides (5 to 55%) germlings, with morphological apoptotic changes characterized by externalization of PS, nuclear condensation, and DNA fragmentation. Moreover, activation of the caspase-like activity was correlated with cell death induced by TCR plus PCZ or ICZ. These changes correlated with elevated intracellular Ca 2؉ and ROS levels and disturbance of mitochondrial potential. We found that PCZ or ICZ in combination with TCR renders Mucorales sensitive to triazoles via apoptotic death. These observations could serve as a new paradigm for the development of new therapeutic strategies.

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Section: Discussionsupporting

confidence: 58%

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

Shirazi

Kontoyiannis

2013

Eukaryot Cell

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“…These peptides include arenicin-1 from the lugworm Arenicola marina [91], pleurocidin from the winter flounder Pleuronectes americanus [92], papiliocin from the butterfly Papilio xuthus [93], melittin from the European honeybee Apis mellifera [94], psacotheasin from larvae of the yellow-spotted long-horned beetle Psacothea hilaris [90] and histatin 5 in saliva from humans [95]. Mammalian lactoferrin from mucosal secretions in humans induces ROS and apoptosis in addition to other mechanisms, such as iron sequestration, K + efflux, cytosolic acidification and changes in the cytosolic membrane potential [96].…”

Section: Novel Ros-inducing Antifungal Agentsmentioning

confidence: 99%

Reactive Oxygen Species-Inducing Antifungal Agents and Their Activity Against Fungal Biofilms

2013

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Invasive fungal infections are associated with very high mortality rates ranging from 20-90% for opportunistic fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Fungal resistance to antimycotic treatment can be genotypic (due to resistant strains) as well as phenotypic (due to more resistant fungal lifestyles, such as biofilms). With regard to the latter, biofilms are considered to be critical in the development of invasive fungal infections. However, there are only very few antimycotics, such as miconazole (azoles), echinocandins and liposomal formulations of amphotericin B (polyenes), which are also effective against fungal biofilms. Interestingly, these antimycotics all induce reactive oxygen species (ROS) in fungal (biofilm) cells. This review provides an overview of the different classes of antimycotics and novel antifungal compounds that induce ROS in fungal planktonic and biofilm cells. Moreover, different strategies to further enhance the antibiofilm activity of such ROS-inducing antimycotics will be discussed.

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“…Indeed, apoptosis can be induced in C. albicans by oxidative stress (6), intracellular acidification, and the antifungal agent amphotericin B (7). Notably, C. albicans cells exhibit apoptotic markers that are similar to those of mammalian cells, including phosphatidylserine externalization, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential dissipation, and DNA condensation and fragmentation (8).…”

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confidence: 99%

Caspofungin Kills Candida albicans by Causing both Cellular Apoptosis and Necrosis

Hao

Cheng

Clancy

et al. 2013

Antimicrob Agents Chemother

148

132

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Caspofungin exerts candidacidal activity by inhibiting cell wall (1,3)-␤-D-glucan synthesis. We investigated the physiologic mechanisms of caspofungin-induced Candida albicans cell death. Apoptosis (programmed cell death) and necrosis were studied after C. albicans SC5314 cells were exposed to caspofungin at 0.06, 0.125, and 0.5 g/ml (0.5؋, 1؋, and 4؋ the MIC, respectively) for 3 h. Caspofungin at 0.125 and 0.5 g/ml reduced cellular viability by >50%, as measured by colony counts and methylene blue exclusion. Apoptosis and necrosis were demonstrated by annexin V and propidium iodide staining for phosphatidylserine externalization and loss of membrane integrity, respectively. At all concentrations of caspofungin, 20 to 25% and 5 to 7% of C. albicans cells exhibited early apoptosis and late apoptosis/necrosis, respectively (P value was not significant [NS]). Necrosis, on the other hand, was significantly greater at 0.125 (43%) and 0.5 (48%) g/ml than at 0.06 g/ml (26%) (P values of 0.003 and 0.003, respectively). The induction of apoptosis at concentrations less than or equal to the MIC was corroborated by dihydrorhodamine 123 (DHR-123) and dihydroethidium (DHE) staining (reactive oxygen species production), JC-1 staining (mitochondrial membrane potential dissipation), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and 4=,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining (DNA damage and nuclear fragmentation). Moreover, electron microscopy of cells exposed to 0.125 g/ml of caspofungin showed hallmark apoptotic features like chromatin margination and condensation and nuclear blebs. Apoptosis was associated with metacaspase 1 activation, as demonstrated by D2R staining. Caspofungin exerts activity against C. albicans by directly killing cells (resulting in necrosis) and causing others to undergo programmed cell death (apoptosis). Apoptosis is initiated at subinhibitory concentrations, suggesting that strategies to target this process may augment the benefits of antifungal agents.C aspofungin and other agents in the echinocandin class of antifungals have assumed an increasingly important role in the therapy of invasive candidiasis (1). These agents are nontoxic and exert potent fungicidal activity against Candida albicans and other Candida spp. Their antifungal activity is achieved through inhibition of (1,3)-␤-D-glucan synthase (2), an enzyme that synthesizes a major constituent of the fungal cell wall. Although the mechanism of activity for the echinocandins is known, the physiological mechanisms by which they cause cell death are not defined. At least two types of mammalian cell death, necrosis and apoptosis, have been described (3). Necrosis is death resulting from direct cellular injury, which is best defined by cell and organelle swelling and lysis (4). Apoptosis, on the other hand, is programmed cell death, the principal morphological feature of which is shrinkage of the cell and its nucleus (3, 4).Over the last decade, there have been a number of reports on apoptosis in yeas...

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Oxidative stress by antimicrobial peptide pleurocidin triggers apoptosis in Candida albicans

Cited by 65 publications

References 38 publications

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

Reactive Oxygen Species-Inducing Antifungal Agents and Their Activity Against Fungal Biofilms

Caspofungin Kills Candida albicans by Causing both Cellular Apoptosis and Necrosis

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