The Interactions between the Antimicrobial Peptide P-113 and Living Cells Shed Light on Mechanisms of Antifungal Activity and Resistance.
Journal
International journal of molecular sciences
Journal Volume
21
Journal Issue
7
Start Page
2654
ISSN
1422-0067
Date Issued
2020-04-10
Author(s)
Cheng, Kuang-Ting
Wu, Chih-Lung
Chih, Ya-Han
Peng, Kuang-Li
Hsu, Su-Ya
Yu, Hui-Yuan
Cheng, Jya-Wei
Abstract
In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, , the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with or its degradation by -secreted proteases that contribute to the fungi's resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.
Subjects
Candida albicans
NMR
antimicrobial peptide
non-natural amino acid
protease
SDGs
Type
journal article