Phenol-Soluble-Modulin-Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug-Resistant Bacteria

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

3 Scopus Citations
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Author(s)

  • Ping Zeng
  • Chen Xu
  • Qipeng Cheng
  • Jun Liu
  • Wei Gao
  • Xuemei Yang
  • Kwok-Yin Wong
  • Kin-Fai Chan

Detail(s)

Original languageEnglish
Pages (from-to)1547-1559
Journal / PublicationChemMedChem
Volume14
Issue number16
Online published30 Jul 2019
Publication statusPublished - 20 Aug 2019
Externally publishedYes

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; Liu, Jun; Gao, Wei; Yang, Xuemei; Wong, Kwok-Yin; Chen, Sheng; Chan, Kin-Fai.

In: ChemMedChem, Vol. 14, No. 16, 20.08.2019, p. 1547-1559.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review