期刊
CHEMMEDCHEM
卷 14, 期 16, 页码 1547-1559出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201900364
关键词
antibiotic-resistant bacteria; antimicrobial peptides; hemolytic activity; phenol-soluble modulins; selective disruption
资金
- Research Grants Council of Hong Kong [15100115, 25100014, C5026-16G]
- Innovation and Technology Commission
- Hong Kong Polytechnic University
Phenol-soluble modulins (PSMs) are a large family of cytolytic peptide toxins produced by Staphylococcus aureus. Based on their amino acid sequences, we have constructed a small library of cationic isoleucine-rich peptides for antimicrobial evaluation. Relative to the parent PSMs, peptide zp3 (GIIAGIIIKIKK-NH2) was found to possess greatly improved physicochemical properties (soluble in water) and antibacterial activity (MIC=8 mu m for E. coli, B. subtilis, and C. freundii) while maintaining low hemolytic activity (m) and cytotoxicity (HEK293 cells IC50>80 mu m). We reasoned that the selective activity of zp3 toward bacterial cells is due to its amphiphilic nature and positive net charge. Moreover, it is difficult for bacteria to develop resistance against zp3. Through microscopic studies of E. coli, we demonstrated that zp3 can penetrate the bacterial membrane, thereby causing leakage of the bacterial cytoplasm. Our findings present a promising antimicrobial peptide lead, which has great potential for further chemical modification.
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