Phenol-Soluble-Modulin-Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug-Resistant Bacteria
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
Author(s)
Detail(s)
Original language | English |
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Pages (from-to) | 1547-1559 |
Journal / Publication | ChemMedChem |
Volume | 14 |
Issue number | 16 |
Online published | 30 Jul 2019 |
Publication status | Published - 20 Aug 2019 |
Externally published | Yes |
Link(s)
Abstract
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 μm for E. coli, B. subtilis, and C. freundii) while maintaining low hemolytic activity (<5 % at 256 μm) and cytotoxicity (HEK293 cells IC50>80 μm). 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.
Research Area(s)
- antibiotic-resistant bacteria, antimicrobial peptides, hemolytic activity, phenol-soluble modulins, selective disruption
Citation Format(s)
Phenol-Soluble-Modulin-Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug-Resistant Bacteria. / Zeng, Ping; Xu, Chen; Cheng, Qipeng et al.
In: ChemMedChem, Vol. 14, No. 16, 20.08.2019, p. 1547-1559.
In: ChemMedChem, Vol. 14, No. 16, 20.08.2019, p. 1547-1559.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review