Fungicide Bac8c triggers attenuation of mitochondrial homeostasis and caspase-dependent apoptotic death

Abstract

Bac8c (RIWVIWRR-NH2), an 8-mer peptide modified from amino acids 4–11 of Bac2a, shows broad-spectrum activity against pathogenic bacteria and yeast, and it has been the focus of attention owing to its low cost of synthesis. Although Bac8c is effective against Candida albicans, its mode of action needs to be investigated further. Bac8c causes yeast cell death in a dose-dependent manner by eliciting the production of reactive oxygen species, thereby attenuating the antioxidant defense system. It is also involved in Ca2+ signaling, and produces apoptotic features, such as phosphatidylserine externalization and DNA fragmentation. Bac8c induces cell death by oxidative stress-dependent apoptotic death via disruption of mitochondrial homeostasis and metacaspase activation. This suggests that the concentration of Bac8c is important for the induction of apoptotic death, which is not necessarily accompanied by cell cycle arrest in C. albicans.