title: 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.
abstract: 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.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Junqiu
authors.initials: J
authors.lastname: Xie
authors.forename: Yuanmei
authors.initials: Y
authors.lastname: Gou
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Kairong
authors.initials: K
authors.lastname: Wang
authors.forename: Xiongli
authors.initials: X
authors.lastname: Yang
authors.forename: Jiexi
authors.initials: J
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects; D004269:DNA, Bacterial / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D057809:HEK293 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D011123:Polyploidy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012867:Skin / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D014981:Xenopus / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C000598874:CPF-C1 peptide, Xenopus clivii; D004269:DNA, Bacterial; D029867:Xenopus Proteins
keywords: CPF-C1; antimicrobial peptides; membrane-active action mode; multidrug-resistant bacteria