1. Antimicrobial activities and membrane-active mechanism of CPF-C1 against multidrug-resistant bacteria, a novel antimicrobial peptide derived from skin secretions of the tetraploid frog Xenopus clivii
Junqiu Xie, Yuanmei Gou, Qian Zhao, Kairong Wang, Xiongli Yang, Jiexi Yan, Wei Zhang, Bangzhi Zhang, Chi Ma, Rui Wang J Pept Sci. 2014 Nov;20(11):876-84. doi: 10.1002/psc.2679. Epub 2014 Aug 6.
Hospital-acquired infections caused by multidrug-resistant bacteria pose significant challenges for treatment, which necessitate the development of new antibiotics. Antimicrobial peptides are considered potential alternatives to conventional antibiotics. The skin of Anurans (frogs and toads) amphibians is an extraordinarily rich source of antimicrobial peptides. CPF-C1 is a typical cationic antimicrobial peptide that was originally isolated from the tetraploid frog Xenopus clivii. Our results showed that CPF-C1 has potent antimicrobial activity against both sensitive and multidrug-resistant bacteria. It disrupted the outer and inner membranes of bacterial cells. CPF-C1 induced both propidium iodide uptake into the bacterial cell and the leakage of calcein from large liposome vesicles, which suggests a mode of action that involves membrane disturbance. Scanning electron microscopy and transmission electron microscopy verified the morphologic changes of CPF-C1-treated bacterial cells and large liposome vesicles. The membrane-dependent mode of action signifies that the CPF-C1 peptide functions freely and without regard to conventional resistant mechanisms. Additionally, it is difficult for bacteria to develop resistance against CPF-C1 under this action mode. Other studies indicated that CPF-C1 had low cytotoxicity against mammalian cell. In conclusion, considering the increase in multidrug-resistant bacterial infections, CPF-C1 may offer a new strategy that can be considered a potential therapeutic agent for the treatment of diseases caused by multidrug-resistant bacteria.
2. New potent antimicrobial peptides from the venom of Polistinae wasps and their analogs
Václav Cerovský, Jirina Slaninová, Vladimír Fucík, Hana Hulacová, Lenka Borovicková, Rudolf Jezek, Lucie Bednárová Peptides. 2008 Jun;29(6):992-1003. doi: 10.1016/j.peptides.2008.02.007. Epub 2008 Feb 19.
Four new peptides of the mastoparan family, characterized recently in the venom of three neotropical social wasps collected in the Dominican Republic, Polistes major major, Polistes dorsalis dorsalis and Mischocyttarus phthisicus were synthesized and tested for antimicrobial potency against Bacillus subtilis, Staphylococcus aureus, Escherichia coli (E.c.) and Pseudomonas aeruginosa, and for hemolytic and mast cells degranulation activities. As these peptides possess strong antimicrobial activity (minimal inhibitory concentration (MIC) values against Bacillus subtillis and E.c. in the range of 5-40 microM), we prepared 40 of their analogs to correlate biological activities, especially antimicrobial, with the net positive charge, hydrophobicity, amphipathicity, peptide length, amino acid substitutions at different positions of the peptide chain, N-terminal acylation and C-terminal deamidation. Circular dichroism spectra of the peptides measured in the presence of trifluoroethanol or SDS showed that the peptides might adopt alpha-helical conformation in such anisotropic environments.
3. Effects and mechanisms of the secondary structure on the antimicrobial activity and specificity of antimicrobial peptides
Xuan-thanh Mai, Jinfeng Huang, Juanjuan Tan, Yibing Huang, Yuxin Chen J Pept Sci. 2015 Jul;21(7):561-8. doi: 10.1002/psc.2767. Epub 2015 Mar 30.
A 15-mer cationic α-helical antimicrobial peptide HPRP-A1 was used as the parent peptide to study the effects of peptide secondary structure on the biophysical properties and biological activities. Without changing the amino acid composition of HPRP-A1, we designed two α-helical peptides with either higher or lower helicity compared with the parent peptide, a β-sheet peptide and a random coiled peptide using de novo design approach. The secondary structures were confirmed by circular dichroism spectroscopy. The three α-helical peptides exhibited comparable antibacterial activities, but their hemolytic activity varied from extreme hemolysis to no hemolysis, which is correlated with their helicity. The β-sheet peptide shows poor antibacterial and strong hemolytic activities. More interestingly, the random coil peptide shows no antibacterial activity against Gram-negative bacteria, weak antibacterial activity against Gram-positive bacteria, and extremely weak hemolytic activity. Bacterial membrane permeabilization was also testified on peptides with different secondary structures. Tryptophan fluorescence experiment revealed that the peptide binding preference to the lipid vesicles for mimicking the prokaryotic or eukaryotic membranes was consistent with their biological activities. With the de novo design approach, we proved that it is important to maintain certain contents of amphipathic secondary structure for a desirable biological activity. We believe that the de novo design approach of relocation of the amino acids within a template sequence could be an effective approach in optimizing the specificity of an antimicrobial peptide.
