Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin
Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin
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DOI：
10.15698/mic2015.11.236
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发表时间：
2015-11-01
期刊：
影响因子：
4.6
通讯作者：
Kontoyiannis, Dimitrios P.
中科院分区：
文献类型：
--
作者：
Shirazi, Fazal;Lewis, Russel E.;Kontoyiannis, Dimitrios P.
我们假设，细胞壁抑制剂米卡芬净（云母）诱导细胞凋亡的MICA敏感（MICA-S）和MICA不敏感（MICA-NS）近平滑念珠菌。分析了MICA-S和MICA-NS C的抗真菌活性和细胞凋亡。在RPMI 1640培养基中于37 ℃暴露于米卡芬净3小时后，通过检测磷脂酰丝氨酸外化（PS）、质膜完整性、活性氧（ROS）产生、线粒体膜电位变化、三磷酸腺苷（ATP）释放和半胱天冬酶样活性来表征细胞凋亡。云母暴露（0.25 ~ 1 mg/L）后，敏感的C.与暴露于米卡芬净（0.5至2 mg/L; P = 0.001）的MICA-NS细胞中仅5-30%的凋亡相比，云母抗真菌活性与凋亡细胞相关，显示出增加的二氢罗丹明-123染色（指示ROS产生）、Rh-123染色（降低的线粒体膜电位）、升高的ATP和增加的后半胱天冬酶活性。总之，云母在MICA-S细胞中是促凋亡的，但在云母-NS C中仍然发挥凋亡作用。近平滑
We hypothesized that the cell wall inhibitor micafungin (MICA) induces apoptosis in both MICA-susceptible (MICA-S) and MICA-nonsusceptible (MICA-NS) Candida parapsilosis. Antifungal activity and apoptosis were analyzed in MICA-S and MICA-NS C. parapsilosis strains following exposure to micafungin for 3 h at 37 degrees C in RPMI 1640 medium. Apoptosis was characterized by detecting phosphatidylserine externalization (PS), plasma membrane integrity, reactive oxygen species (ROS) generation, mitochondrial membrane potential changes, adenosine triphosphate (ATP) release, and caspase-like activity. Apoptosis was detected in MICA exposed (0.25 to 1 mg/L) susceptible C. parapsilosis strains and was associated with apoptosis of 20-52% of analyzed cells versus only 5-30% of apoptosis in MICA-NS cells exposed to micafungin (0.5 to 2 mg/L; P = 0.001). The MICA antifungal activity was correlated with apoptotic cells showing increased dihydrorhodamine-123 staining ( indicating ROS production), Rh-123 staining (decreased mitochondrial membrane potential), elevated ATP, and increased metacaspase activity. In conclusion, MICA is pro-apoptotic in MICA-S cells, but still exerts apoptotic effects in MICA -NS C. parapsilosis.