Antimicrobial peptides (AMPs) are promising therapeutic agents for treating antibiotic-resistant bacterial infections. Previous studies showed that magainin 2 (isolated from African clawed fogs Xenopus laevis) has antimicrobial activity against gram-positive and gram-negative bacteria. The present study was conducted to investigate the antibacterial activity of magainin 2 against Acinetobacter baumannii. Magainin 2 showed excellent antibacterial activity against A. baumannii strains and high stability at physiological salt concentrations. This peptide was not cytotoxic towards HaCaT cells and showed no hemolytic activity. Biofilm inhibition and elimination were significantly induced in all A. baumannii strains exposed to magainin 2. We confirmed the mechanism of magainin 2 on the bacterial outer and inner membranes. Collectively, these results suggest that magainin 2 is an effective antimicrobial and antibiofilm agent against A. baumannii strains.

Hp1404, identified from the venom of the scorpion Heterometrus petersii, displays antimicrobial activity with cytotoxicity. Several synthetic peptides were designed based on the parent peptide Hp1404 to reduce cytotoxicity and improve activity (deletion of glycine and phenylalanine, substitution with leucine and lysine). The analogue peptides generated comprised 12 amino acids and displayed amphipathic α-helical structures, with higher hydrophobic moments and net positive charge than those of the Hp1404. The analogues showed less hemolytic and toxic effects toward mammalian cells than the Hp1404, especially Hp1404-T1e, which exhibited particularly potent antibacterial and antibiofilm activities against multidrug-resistant Pseudomonas aeruginosa (MRPA) strains. The analogue peptide Hp1404-T1e was more stable against salt and trypsin than the Hp1404. Hp1404's mechanism of action involves binding to lipopolysaccharide (LPS), thereby killing bacteria through membrane disruption. Hp1404-T1e kills bacteria more rapidly than Hp1404 and not only seems to bind more strongly to LPS but may also be able to enter bacterial cells and interact with their DNA. Additionally, Hp1404-T1e can effectively kill bacteria in vivo. The results of this study indicate that Hp1404-T1e not only displays antimicrobial activity, but is also functional in physiological conditions, confirming its potential use as an effective therapeutic agent against MRPA.

Antimicrobial peptides have attracted attention as alternatives to conventional antibiotics. previously, a novel antimicrobial peptide, melectin, consisting of 18 amino acids was isolated from the venom of a bee, Melecta albifrons. Here, we investigated the antibacterial activity of melectin against drugresistant bacteria. Melectin showed broad-spectrum antimicrobial activity but low cytotoxicity and no hemolytic activity. Melectin maintained its antimicrobial activity at physiological salt concentrations. Melectin is an α-helical structure that binds to the bacterial membrane via electrostatic interactions and kills bacteria in a short time by bacterial membrane targeting. collectively, our results suggest that melectin has antibacterial activity and anti-inflammatory activity. Excessive use of antibiotics leads to the development of drug-resistant bacteria, which threatens human health 1. Drug-resistant bacteria develop rapidly, while novel antibiotics are discovered at a slower rate. To combat drug-resistant bacteria, new antibiotics must be developed. Antimicrobial peptides (AMPs), known as host defense peptides, consist of short amino acid sequences containing both positively charged and hydrophobic amino acids 2. AMPs are attractive candidates as therapeutic agents, as they can kill a broad range of bacteria including antibiotic-resistant strains and do not tend to develop drug resistance 3. Most AMPs display antimicrobial activity by disrupting the bacterial membrane. The cationic charge of AMPs enables an electrostatic interaction with the negatively charged bacterial membrane. The cytoplasmic membrane of bacteria is rich in phospholipids phosphatidylglycerol, cardiolipin, and phosphatidylserine which have negatively charged head groups and bind to positively charged AMPs. Additionally, the presence of lipoteichoic acid (LTA) of gram-positive bacteria and lipopolysaccharide (LPS) of gram-negative bacteria acts as a lipophilic anchor 4,5. AMPs can replace divalent cations such as Mg 2+ and Ca 2+ bound to LPS, causing membrane disruption and eventually bacterial death 6. Some AMPs penetrate the bacterial membrane and kill bacteria without inducing bacterial membrane permeabilization. These AMPs attack DNA and RNA to inhibit protein synthesis 7. Examples of these AMPs include buforin2 8 and indolicidin 9. The salt sensitivity of AMPs is a major limitation to the development of AMPs as treatment agents 10. AMPs interact electrostatically with the microbial membrane in a salt-sensitive manner. Human body fluid has a high salt concentration which interferes with the antimicrobial activity of AMPs 11. Therefore, it is necessary to develop a peptide that maintains its antimicrobial activity even at physiological salt concentration. Bee venoms contain diverse active compounds, including polypeptides, enzymes, and amino acids 12. Bee venom therapy is the therapeutic application of bee venom. The compounds in bee venom are used as traditional medicines for anti-arthritis and pain relief 13. Various antimicrobial pep...

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The abuse of antibiotics for disease treatment has led to the emergence of multidrug resistant bacteria. Antimicrobial peptides, found naturally in various organisms, have received increasing interest as alternatives to conventional antibiotics because of their broad spectrum antimicrobial activity and low cytotoxicity. In a previous report, Macropin, isolated from bee venom, exhibited antimicrobial activity against both gram-positive and negative bacteria. In the present study, Macropin was synthesized and its antibacterial and anti-biofilm activities were tested against bacterial strains, including gram-positive and negative bacteria, and drug resistant bacteria. Moreover, Macropin did not exhibit hemolytic activity and cytotoxicity to keratinocytes, whereas Melittin, as a positive control, showed very high toxicity. Circular dichroism assays showed that Macropin has an α-helical structure in membrane mimic environments. Macropin binds to peptidoglycan and lipopolysaccharide and kills the bacteria by disrupting their membranes. Moreover, the fractional inhibitory concentration index indicated that Macropin has additive and partially synergistic effects with conventional antibiotics against drug resistant bacteria. Thus, our study suggested that Macropin has potential for use of an antimicrobial agent for infectious bacteria, including drug resistant bacteria.