Design and characterization of short hybrid antimicrobial peptides from pEM‐2, mastoparan‐VT1, and mastoparan‐B

Abstract

Antimicrobial peptides are considered to be excellent templates for designing novel antibiotics because of their broad-spectrum antimicrobial activity and their low prognostic to induce antibiotic resistance. In this study, for the first time, a series of short hybrid antimicrobial peptides combined by different fragments of venom-derived alpha-helical antimicrobial peptides pEM-2, mastoparan-VT1, and mastoparan-B were designed with the intent to improve the therapeutic index of the parental peptides. Short hybrid antimicrobial peptides PV, derived from pEM-2 and mastoparan-VT1, was found to possess the highest antibacterial, hemolytic, and cytotoxic activity. Short hybrid antimicrobial peptides PV3, derived from pEM-2 and three fragments of mastoparan-VT1, showed more than threefold improvement in therapeutic index compared with parental peptides pEM-2 and mastoparan-VT1. PV had the highest antimicrobial activity in stability studies. Except BVP, designed based on all three parental peptides, the other short hybrid antimicrobial peptides at their minimal inhibitory concentration and 2× minimal inhibitory concentration required less than 120 and 60 min to reduce >3log10 the initial inoculum, respectively. All peptides had membrane-disrupting activity in a time-dependent manner. Collectively, this study highlights the potential for rational design of improved short hybrid antimicrobial peptides such as PV3 that was an ideal candidate for further assessment with the ultimate purpose of development of effective antimicrobial agents.

Membrane‐active peptide PV3 efficiently eradicates multidrug‐resistant Pseudomonas aeruginosa in a mouse model of burn infection

“…The CD spectra of peptide PV3 indicate that it adopts an alpha‐helical structure in a hydrophobic membrane‐mimicking environment. This conformation of peptide PV3 was consistent with our prediction of its secondary structures, as previously described . Based on confocal laser‐scanning microscopy technique, it appears that the main target of FITC‐labeled PV3 derivative is the bacterial membrane.…”

“…We have previously reported on a series of SHAMPs and identified PV3 as a peptide with the most appropriate therapeutic index . We further investigated its antibacterial potential by studying the efficacies in vitro and in vivo of peptide PV3 against a clinically isolated MDR P. aeruginosa isolate.…”

Alignment‐based design and synthesis of new antimicrobial Aurein‐derived peptides with improved activity against Gram‐negative bacteria and evaluation of their toxicity on human cells

“…After incubation for 0, 15, 30, 60, 120, 150, and 180 min at 37°C, samples were serially diluted and plated in triplicate onto MHA plates. CFU was counted after 24 hr of incubation of plates at 37°C (Memariani et al, ). In this study, streptomycin and penicillin were used as antibiotic controls.…”

AurH1: a new heptapeptide derived from Aurein1.2 antimicrobial peptide with specific and exclusive fungicidal activity

“…Briefly, logarithmically growing C. albicans ATCC 10231 were suspended to fresh SDB, adjusted to 5 × 10 5 CFU/mL, and added to the medium containing the peptides at concentrations equivalent to 1×MIC and 2×MIC. Following incubation for 0, 4, 8, 12, and 24 hours at 37°C, samples were serially diluted and plated in triplicate onto SDA plates . CFU was counted after 24 hours of plate incubation at 37°C.In this test, nystatin and fluconazole were used as antibiotic controls.…”