Mechanism of action and in vitro activity of short hybrid antimicrobial peptide PV3 against Pseudomonas aeruginosa.
Antimicrobial peptides are attractive candidates for developing novel therapeutic agents, since they are lethal to a broad spectrum of pathogens and have a unique low tendency for resistance development. In this study, mechanism of action and in vitro anti-pseudomonal activity of previously designed short hybrid antimicrobial peptide PV3 were investigated. Compared to ceftazidime, PV3 had not only higher antibacterial activity but also faster bactericidal activity. PV3 reduced biofilm biomass and viability of biofilm embedded bacteria in a concentration-dependent manner. Although the antimicrobial activity of PV3 was reduced in Mueller-Hinton broth (MHB) containing human serum, it was still active enough to eradication of bacteria at low concentrations. Compared with standard condition (MHB only), there was no significant decrease in antibacterial activity of PV3 against P. aeruginosa strains under 150 mM NaCl (p = 0.615) and 1 mM MgCl2 (p = 0.3466). Fluorescence microscopy and field emission scanning electron microscopy further indicated that PV3 killed bacteria by disrupting the cell membrane. Since PV3 has potent anti-pseudomonal activity and has little cytotoxicity in vitro, it seems plausible that the peptide should be further investigated with animal studies to support future pharmacological formulations and potential topical applications.
Biotechnology Research Center, Medical Biotechnology Department, Venom and Biotherapeutics Molecules Lab, Pasteur Institute of Iran, Tehran, Iran.
Hamed
H
Memariani
Biotechnology Research Center, Medical Biotechnology Department, Venom and Biotherapeutics Molecules Lab, Pasteur Institute of Iran, Tehran, Iran.
Delavar
D
Shahbazzadeh
INSERM, Aix-Marseille Université, UMRs 1097, Parc scientifique et technologique de Luminy, Marseille, France.
Jean-Marc
JM
Sabatier
Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Mojtaba
M
Memariani
Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Ali
A
Karbalaeimahdi
Biotechnology Research Center, Medical Biotechnology Department, Venom and Biotherapeutics Molecules Lab, Pasteur Institute of Iran, Tehran, Iran. Electronic address: k_bagheri@pasteur.ac.ir.
Kamran Pooshang
KP
Bagheri
D000328:Adult; D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002056:Burns / Q000382:microbiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012910:Snake Venoms / Q000235:genetics; D014862:Wasp Venoms / Q000235:genetics; D055815:Young Adult
D023181:Antimicrobial Cationic Peptides; D011993:Recombinant Fusion Proteins; D012910:Snake Venoms; D014862:Wasp Venoms
Antimicrobial peptides; Biofilm; Membrane-disrupting activity; Pseudomonas aeruginosa