In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria

Abstract

Background Melittin is one of the most studied antimicrobial peptides, and several in vitro experiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap between in vitro and in vivo studies. Methods In the first step, in vitro toxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR) Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and KPC-producing Klebsiella pneumonia (KPC-KP) pathogens were tested using both in vitro and in vivo methods. Results Melittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50 value of 4.98 mg/kg in BALB/c mice. In vitro antimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads. Conclusions These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.

Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ25–35 in In Vitro and In Vivo Models

“…On day 1, except for the naïve group which received PBS ICV., all mice were injected with 5 µL PBS solution containing 5 μg of Aβ 25–35 . A melittin maximum safety dosage of approximately 1.5 mg/kg was previously determined [ 25 , 26 , 27 ]. Therefore, we used 1.5 mg/kg melittin, and another dosage, 0.15 mg/kg melittin, was to study any possible dosage-dependent effect.…”

Gramicidin S and melittin: potential anti-viral therapeutic peptides to treat SARS-CoV-2 infection

“…Not much scientific evidences or reports are available so far for the antiviral activity of the gramicidin S. Gramicidin S showed cell cytotoxicity (CC50) at 18.7 μg/ml in HT-29 cells 25 . Melittin showed CC50 of 6.45 μg/ml in C654 cells 26 .…”

Melittin-Based Nano-Delivery Systems for Cancer Therapy

“…Studies examining the antimicrobial activity of MEL in vivo [ 61 ] have found an increased mortality rate in mice directly injected with MEL. LD 50 value of intraperitoneal MEL to mice is around 5 mg/kg, and drops to about 3 mg/kg via intravenous injection [ 62 , 63 , 64 ]. Preclinical and clinical research on BV therapy has indicated that the main adverse reactions of MEL include allergic reactions and pain at the administration site [ 65 , 66 ], which limits BV’s application in acupuncture therapies.…”