Two optimized antimicrobial peptides with therapeutic potential for clinical antibiotic-resistant Staphylococcus aureus.

Abstract

The rapid increase of Methicillin-resistant Staphylococcus aureus (MRSA) infections and the cross-resistance of MRSA to other antibiotics create an urgent demand for new therapeutic agents. Antimicrobial peptides (AMPs) are one of the most promising options for next-generation antibiotics. In this study, novel peptides were designed based on antimicrobial peptide fragments derived from Aristicluthys nobilia interferon-I to promote anti-MRSA activity and decrease adverse effects. Design strategies included substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote amphipathicity. Two designed peptides, P5 (YIRKIRRFFKKLKKILKK-NH2) and P9 (SYERKINRHFKTLKKNLKKK-NH2), showed potent antimicrobial activities against both sensitive Staphylococcus aureus clinical isolates and MRSA strains without significant hemolysis or cytotoxicity to human hemocytes and renal epithelial cells. Scanning Electronic Microscopy (SEM) and qRT-PCR were employed to investigate the effects of P5 and P9 on S. aureus biofilm formation, morphology, and virulence-related gene expression. P5 and P9 significantly inhibited the biofilm and destroyed the cell membrane integrity, in addition to down-regulating several virulence factor genes and biofilm formation-related genes including spa, hld, and sdrC. P5 and P9 could be promising candidate antibacterial agents for the treatment of MRSA infections.

• Authors: Chunlei Li, Chengguang Zhu, Biao Ren, Xin Yin, Sang Hee Shim, Yue Gao, Jianhua Zhu, Peipei Zhao, Changheng Liu, Rongmin Yu, Xuekui Xia, Lixin Zhang
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 183 Pg. 111686 (Dec 01 2019) ISSN: 1768-3254 [Electronic] France
• PMID: 31520928 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Chemical References

• Anti-Infective Agents
• Antimicrobial Cationic Peptides

Topics

• Anti-Infective Agents (chemistry, pharmacology)
• Antimicrobial Cationic Peptides (chemistry, pharmacology)
• Biofilms (drug effects)
• HEK293 Cells
• Hemolysis (drug effects)
• Humans
• Methicillin-Resistant Staphylococcus aureus (drug effects)
• Staphylococcal Infections (drug therapy)