title: Micafungin triggers caspase-dependent apoptosis in Candida albicans and Candida parapsilosis biofilms, including caspofungin non-susceptible isolates.
abstract: Candida biofilms play an important role in infections associated with medical devices and are resistant to antifungals. We hypothesized that the echinocandin micafungin (MICA) exerts an enhanced antifungal activity against caspofungin (CAS)-susceptible (CAS-S) and CAS-non-susceptible (CAS-NS) Candida albicans and Candida parapsilosis which is at least in part through apoptosis, even in the biofilm environment. Apoptosis was characterized by detecting reactive oxygen species (ROS) accumulation, depolarization of mitochondrial membrane potential (MMP), DNA fragmentation, lack of plasma membrane integrity, and metacaspase activation following exposure of Candida biofilm to MICA for 3h at 37°C in RPMI 1640 medium. The minimum inhibitory concentration was higher for CAS (2.0-16.0 μg/mL) than for MICA (1.0-8.0 μg/mL) for Candida biofilms. Elevated intracellular ROS levels and depolarization of MMP was evident in CAS-S C. albicans (3.0-4.2 fold) and C. parapsilosis (4.8-5.4 fold) biofilms compared with CAS-NS (1.2 fold) after exposure to MICA (0.25x-1xMIC). Elevated intracellular ROS levels and depolarization of MMP was evident in CAS-S C. albicans (3.0-4.2 fold) and C. parapsilosis (4.8-5.4 fold) biofilms compared with CAS-NS (1.2 fold) after exposure to MICA (0.25x-1xMIC). Finally higher ß-1, 3 glucan levels were seen in sessile cells compared to planktonic cells, especially in CAS-NS strains. MICA treatment might induce a metacaspase-dependent apoptotic process in biofilms of both CAS-S C. albicans and C. parapsilosis, and to some degree in CAS-NS strains.
authors.affiliation: a Department of Infectious Diseases; Infection Control and Employee Health ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
authors.forename: F
authors.initials: F
authors.lastname: Shirazi
authors.forename: D P
authors.initials: DP
authors.lastname: Kontoyiannis
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology / Q000648:ultrastructure; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D020169:Caspases / Q000378:metabolism*; D000077336:Caspofungin; D053938:DNA Fragmentation; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology*; D055666:Lipopeptides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D017382:Reactive Oxygen Species; D020169:Caspases; D000077336:Caspofungin; D000077551:Micafungin
keywords: Apoptosis; biofilms; caspofungin; micafungin; reactive oxygen species