Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata
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 cas...
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Mazandaran University of Medical Sciences
2019-06-01
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Series: | Current Medical Mycology |
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Online Access: | http://cmm.mazums.ac.ir/article_90412_765a4dd95eb7b293fa99a8117ba20cdf.pdf |
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author | Parisa Aryamloo Hossein Asgarian-Omran Narges Aslani Hadi Hossein-Nataj Tahereh Shokohi Hamid Badali Mojtaba Nabili Atefeh Abdollahi Gohar Maryam Moazeni |
author_facet | Parisa Aryamloo Hossein Asgarian-Omran Narges Aslani Hadi Hossein-Nataj Tahereh Shokohi Hamid Badali Mojtaba Nabili Atefeh Abdollahi Gohar Maryam Moazeni |
author_sort | Parisa Aryamloo |
collection | DOAJ |
description | 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.<br /> <br /> 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.<br /> <br /> 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).<br /> <br /> 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.<br /> |
first_indexed | 2024-04-13T04:34:31Z |
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language | English |
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spelling | doaj.art-b944ce771507447996bbc0db02b395d52022-12-22T03:02:13ZengMazandaran University of Medical SciencesCurrent Medical Mycology2423-34392423-34202019-06-015291510.18502/cmm.5.2.115590412Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrataParisa Aryamloo0Hossein Asgarian-Omran1Narges Aslani2Hadi Hossein-Nataj3Tahereh Shokohi4Hamid Badali5Mojtaba Nabili6Atefeh Abdollahi Gohar7Maryam Moazeni81Student Research Committee, Mazandaran University of Medical Sciences, Sari, IranDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IranInfectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IranInvasive Fungi Research Centre, Mazandaran University of Medical Sciences, Sari, IranInvasive Fungi Research Centre, Mazandaran University of Medical Sciences, Sari, IranDepartment of Medical Laboratory Sciences, Sari Branch, Islamic Azad University, Sari, IranStudent Research Committee, Mazandaran University of Medical Sciences, Sari, IranInvasive Fungi Research Centre, Mazandaran University of Medical Sciences, Sari, IranBackground 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.<br /> <br /> 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.<br /> <br /> 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).<br /> <br /> 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.<br />http://cmm.mazums.ac.ir/article_90412_765a4dd95eb7b293fa99a8117ba20cdf.pdfcandida glabratacaspofunginflow cytometrymca1nuc1 |
spellingShingle | Parisa Aryamloo Hossein Asgarian-Omran Narges Aslani Hadi Hossein-Nataj Tahereh Shokohi Hamid Badali Mojtaba Nabili Atefeh Abdollahi Gohar Maryam Moazeni Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata Current Medical Mycology candida glabrata caspofungin flow cytometry mca1 nuc1 |
title | Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata |
title_full | Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata |
title_fullStr | Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata |
title_full_unstemmed | Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata |
title_short | Cellular apoptosis: An alternative mechanism of action for caspofungin against Candida glabrata |
title_sort | cellular apoptosis an alternative mechanism of action for caspofungin against candida glabrata |
topic | candida glabrata caspofungin flow cytometry mca1 nuc1 |
url | http://cmm.mazums.ac.ir/article_90412_765a4dd95eb7b293fa99a8117ba20cdf.pdf |
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