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Phenol‐Soluble‐Modulin‐Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug‐Resistant Bacteria
Author(s) -
Zeng Ping,
Xu Chen,
Cheng Qipeng,
Liu Jun,
Gao Wei,
Yang Xuemei,
Wong KwokYin,
Chen Sheng,
Chan KinFai
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900364
Subject(s) - antimicrobial , chemistry , antimicrobial peptides , peptide , multiple drug resistance , amphiphile , bacteria , microbiology and biotechnology , cytotoxicity , antibacterial activity , staphylococcus aureus , bacillus subtilis , teichoic acid , biochemistry , biology , in vitro , antibiotics , organic chemistry , genetics , copolymer , polymer
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‐NH 2 ) was found to possess greatly improved physicochemical properties (soluble in water) and antibacterial activity (MIC=8 μ m for E . coli , B . subtilis , and C . freundii ) while maintaining low hemolytic activity (<5 % at 256 μ m ) and cytotoxicity (HEK293 cells IC 50 >80 μ 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.