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

Ping Zeng, Chen Xu, Qipeng Cheng, Jun Liu, Wei Gao, Xuemei Yang, Kwok Yin Wong, Sheng Chen (Corresponding Author), Kin Fai Chan (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1547-1559
Number of pages13
Issue number16
Publication statusPublished - 1 Jan 2019


  • antibiotic-resistant bacteria
  • antimicrobial peptides
  • hemolytic activity
  • phenol-soluble modulins
  • selective disruption

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry


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