Mastoparan B

The high mortality associated with invasive fungal infections, narrow spectrum of available antifungals, and increasing evolution of antifungal resistance necessitate the development of alternative therapies. Host defense peptides are regarded as the first line of defense against microbial invasion in both vertebrates and invertebrates. In this work, we investigated the effectiveness of four naturally occurring pore-forming antimicrobial peptides (melittin, magainin 2, cecropin A, and mastoparan B) against a panel of clinically relevant pathogens, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. We present data on the antifungal activities of the four pore-forming peptides, assessed with descriptive statistics, and their cytocompatibility with cultured human cells. Among the four peptides, mastoparan B (MB) displayed potent antifungal activity, whereas cecropin A was the least potent. We show that MB susceptibility of phylogenetically distant non-candida albicans can vary and be described by different intrinsic physicochemical parameters of pore-forming α-helical peptides. These findings have potential therapeutic implications for the design and development of safe antifungal peptide-based drugs.

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.

Mastoparan B (MP-B), an amphiphilic alpha-helical peptide isolated from hornet venom, and its Ala-substituted analogs were examined for their effectiveness on phospholipase D (PLD) activity in L1210 cells. PLD activity was determined by measuring phosphatidylethanol produced from [3H]myristate-labelled cells in the presence of ethanol. PLD activity was stimulated by MP-B, 4MP-B (Lys4-->Ala), and 12MP-B (Lys12-->Ala), but not by 3MP-B (Leu3-->Ala) and 9MP-B (Trp9-->Ala). Other MPs including mastoparan 7 also stimulated the PLD activity, but inactive mastoparan 17 did not. The stimulatory effect of various MP analogs could be correlated with their alpha-helical contents. The PLD activity stimulated by MP-B was not affected by G-protein blocking chemicals. The extent of PLD stimulation by various MP-Bs, as well as by digitonin and beta-escin, correlated with the permeability of the membrane to ethidium bromide. These results suggest that the stimulation of PLD activity by MP-B in L1210 cells is probably coupled with membrane perturbation brought about by the peptide.