Lactoferricin B like peptide triggers mitochondrial disruption ‐mediated apoptosis by inhibiting respiration under nitric oxide accumulation in Candida albicans

AbstractNitric oxide (NO) is a potentially powerful weapon againstCandida albicans, and the regulation of intracellular NO levels is therefore important for controlling its physiological functions. Lactoferricin B like peptide (LBLP) is a 23 ‐mer antimicrobial peptide (AMP) derived from theScolopendra subspinipes mutilans. We confirmed that LBLP treatment led to the generation of endogenous NO inC. albicans, which was associated with the NO synthase pathway. Here, we examined the antifungal activity of LBLP with focus on intracellular NO. Total glutathione levels were measured to evaluate cellular defense capacity against NO. LBLP decreased total glutathione levels, leading to nitrosative stress. LBLP also inhibited mitochondrial respiration and altered the NAD+/NADH ratios. Inhibition of mitochondrial respiration induced mitochondrial membrane depolarization, thus leading to calcium homeostasis disruption and mitochondrial superoxide anion accumulation. Consequently, treatment ofC. albicans with LBLP resulted in apoptosis. These physiological changes were attenuated when NO generation was inhibited. Our data strongly indicate that LBLP mediates apoptosis by affecting intracellular NO homeostasis. These results on antifungal activity of LBLP and its mechanism indicate the therapeutic promise of this AMP and support the role of NO in cell death regulation.

Source: IUBMB Life - April 7, 2020 Category: Research Authors: Suhyun Kim, Jae Sam Hwang, Dong Gun Lee Tags: RESEARCH COMMUNICATION Source Type: research