title: Micafungin induced apoptosis inCandida parapsilosisindependent of its susceptibility to micafungin.
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-NSC. parapsilosisstrains 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) susceptibleC. parapsilosisstrains 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 -NSC. parapsilosis.
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M D Anderson Cancer Center, Houston, TX, USA.
authors.forename: Fazal
authors.initials: F
authors.lastname: Shirazi
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M D Anderson Cancer Center, Houston, TX, USA. ; Current Address: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Russel E
authors.initials: RE
authors.lastname: Lewis
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M D Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
keywords: apoptosis; metacaspase; micafungin; reactive oxygen species