Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin

Authors:

Fazal Shirazi1, Russel E. Lewis1,2, Dimitrios P. Kontoyiannis1

doi: 10.15698/mic2015.11.236
Volume 2, pp. 445 to 450, published 23/10/2015.

PDF Download PubMed Link
Affiliations:

1 Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M D Anderson Cancer Center, Houston, TX, USA.

2 Current Address: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Keywords: 

apoptosis, micafungin, metacaspase, reactive oxygen species

Corresponding Author(s):

Dimitrios P. Kontoyiannis, Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard; Houston, TX 77030, USA dkontoyi@mdanderson.org

Conflict of interest statement:

D.P.K. has received research support and honoraria from Pfizer; Astellas Pharma US, Inc.; Merck & Co., Inc.; T2 Biosystems. F.S. and R.E.L. have no conflicts of interest.

Please cite this article as:

Fazal Shirazi, Russel E. Lewis, Dimitrios P. Kontoyiannis (2015). Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin. Microbial Cell2(11): 445-450.

© 2015 Shirazi et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

We hypothesized that the cell wall inhibitor micafungin (MICA) induces apoptosis in both MICA-susceptible (MICA-S) and MICA–non-susceptible (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°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.