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. 2019 Jun;5(2):9-15.
doi: 10.18502/cmm.5.2.1155.

Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata

Parisa Aryamloo  1 , Hossein Asgarian-Omran  2   3 , Narges Aslani  4 , Hadi Hossein-Nataj  2 , Tahereh Shokohi  5   6 , Hamid Badali  5   6 , Mojtaba Nabili  7 , Atefeh Abdollahi Gohar  1 , Maryam Moazeni  5   6
Affiliations

Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata

Parisa Aryamloo et al. Curr Med Mycol. 2019 Jun.

Abstract

Background and purpose: Although the mechanism of action for echinocandins is known, the physiological mechanisms by which these antifungal agents cause cell death via the classical apoptotic pathways are not well-defined yet. Regarding this, the present study aimed to evaluate the mechanisms of caspofungin-induced Candida glabrata cell death.

Materials and methods: For the purpose of the study, the minimum inhibitory concentration (MIC) of caspofungin against C. glabrata (ATCC 90030) was determined using the broth microdilution reference method (CLSI M27-A2 and M27-S4). The annexin V and propidium iodide staining was performed to determine the way through which caspofungin acts against C. glabrata (i.e., through the induction of apoptosis and/or necrosis). Additionally, the possible effect of caspofungin on inducing the expression of two apoptotic genes, namely MCA1 and NUC, was studied using the real-time polymerase chain reaction assay.

Results: According to the obtained MIC value (0.5 µg/mL), C. glabrata, exposed to 0.25, 0.5, and 1 µg/mL of caspofungin, exhibited the features of late apoptosis/necrosis after 18 h of incubation. Furthermore, the use of 0.25, 0.5, and 1 µg/ml caspofungin induced apoptosis (early/late) in 14.67%, 17.04%, and 15.89% of the cells, respectively. The results showed a significant difference between the percentages of early-apoptotic cells at the three concentrations (P<0.05). In addition, the rate of necrosis was significantly greater than that of apoptosis in response to caspofungin. Accordingly, necrosis occurred in 71.26%, 71.26%, and 61.26% of the cells at the caspofungin concentrations of 0.25, 0.5, and 1 µg/mL, respectively (P<0.05). The analysis of the data in the REST software demonstrated a significant increase in the expression of MCA1 and NUC1 genes (P<0.05).

Conclusion: As the findings of the present study indicated, caspofungin promoted both necrosis and apoptosis of C. glabrata cells at concentrations higher than or equal to the MIC value.

Keywords: Candida glabrata; Caspofungin; Flow cytometry; MCA1; NUC1.

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Conflict of interest statement

The authors declare no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Cell apoptosis determined by annexin V-fluorescein isothiocyanate staining
Figure 2
Figure 2
Effect of different concentrations of caspofungin on early apoptosis, late apoptosis, and necrosis
Figure 3
Figure 3
Nuclear fragmentation as demonstrated by diamidino-2-phenylindole dihydrochloride staining
Figure 4
Figure 4
Rate of the expression of two major apoptotic genes
See this image and copyright information in PMC

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