melitten and Staphylococcal-Infections

The antibacterial activity of melittin (Mel) on. The effective inhibitory activity of Mel on skin pathogens was demonstrated. Among the tested strains, VISA was most susceptible to Mel. Regarding to its function, Mel targeted the bacterial cell envelope and disrupted cell membrane integrity. Mel-loaded NISVs were successfully fabricated with a nano-size of 120-200 nm and entrapment efficiency of greater than 90%. Moreover, Mel-loaded NISVs were taken up and accumulated in the intracellular space. Meanwhile, Mel was released and distributed throughout the cytosol and nucleus. Mel-loaded NISVs efficiently inhibited the growth of bacteria, particularly MRSA and VISA. Importantly, they not only penetrated epidermal and dermal skin layers, but also reduced the bacterial growth in infected skin.. Mel-loaded NISVs have a great potential to exhibit antibacterial activity. Therapeutic application of Mel-loaded NISVs could be further developed as an alternative platform for the treatment of skin infection via dermal and transdermal delivery.

Topics: Animals; Anti-Bacterial Agents; Humans; Melitten; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcal Skin Infections; Staphylococcus aureus; Swine; Vancomycin-Resistant Staphylococcus aureus

Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) require the development of new and effective topical antibiotics. In this context, melittin, the main component of apitoxin, has a potent antibacterial effect. However, little is known regarding the anti-inflammatory potential this peptide in infection models, or its ability to induce clinically important resistance. Here, we aimed to conduct an in-depth characterization of the antibacterial potential of melittin in vitro and evaluate the pharmaceutical potential of an ointment containing melittin for the treatment of non-surgical infections induced by MRSA. The minimum inhibitory concentration of melittin varied from 0.12 to 4 μM. The antibacterial effect was mainly bactericidal and fast (approximately 0.5 h after incubation) and was maintained even in stationary cells and mature MRSA biofilms. Melittin interacts synergistically with beta-lactams and aminoglycosides, and its ability to form pores in the membrane reverses the resistance of vancomycin-intermediate Staphylococcus aureus (VISA) to amoxicillin, and vancomycin. Its ability to induce resistance in vitro was absent, and melittin was stable in several conditions often associated with infected wounds. In vivo, aointment containing melittin reduced bacterial load and the content of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1 beta. Collectively, these data point to melittin as a potential candidate for topical formulations aimed at the treatment of non-surgical infections caused by MRSA.

Topics: Anti-Bacterial Agents; Humans; Melitten; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus

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.. 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.. These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Cell Line; Drug Resistance, Bacterial; Hemolysis; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Melitten; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Microbial Sensitivity Tests; Peritonitis; Sepsis; Staphylococcal Infections

The antibacterial activities of apitoxin, a venom produced by Apis mellifera bee, and melittin, an antimicrobial peptide from apitoxin, were tested against planktonic and biofilm states of Staphylococcus aureus methicillin-resistant (MRSA), including clinical, and enterotoxin-producing isolates. Also, the synergism of apitoxin and melittin in combination with oxacillin were evaluated as well. The induced morphological changes on S. aureus cells of both products were detected by transmission electronic microscopy (TEM). The minimum inhibitory concentration (MIC) values were 7.2 μg/mL, and 6.7 μg/mL, for apitoxin and melittin, respectively. The minimum bactericidal concentration (MBC) values were 28.7 μg/mL, and 26 μg/mL for apitoxin and melittin, respectively. The time-kill curve assays of apitoxin or melittin with oxacillin exhibited bactericidal synergism against MRSA isolates. TEM images showed cell distortion, cell disintegration with leakage of cytoplasmic content and loss of cytoplasm content. However, apitoxin and melittin did not interfere with staphylococcal enterotoxin production or release. Thus, apitoxin and melittin are potential agents against MRSA that can serve as possible models for new antibacterial drugs.

Topics: Animals; Anti-Bacterial Agents; Bee Venoms; Bees; Biofilms; Drug Synergism; Humans; Melitten; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxacillin; Staphylococcal Infections

Topics: Anti-Bacterial Agents; Clindamycin; Exfoliatins; Humans; Melitten; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Virulence Factors

Methicillin‑resistant Staphylococcus aureus (MRSA) is difficult to treat using available antibiotic agents. Honeybee venom has been widely used as an oriental treatment for several inflammatory diseases and bacterial infections. The venom contains predominantly biologically active compounds, however, the therapeutic effects of such materials when used to treat MRSA infections have not been investigated extensively. The present study evaluated bee venom and its principal active component, melittin, in terms of their antibacterial activities and in vivo protection against MRSA infections. In vitro, bee venom and melittin exhibited comparable levels of antibacterial activity, which was more marked against MRSA strains, compared with other Gram‑positive bacteria. When MRSA‑infected mice were treated with bee venom or melittin, only the latter animals were successfully rescued from MRSA‑ induced bacteraemia or exhibited recovery from MRSA‑infected skin wounds. Together, the data of the present study demonstrated for the first time, to the best of our knowledge, that melittin may be used as a promising antimicrobial agent to enhance the healing of MRSA‑induced wounds.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bee Venoms; Bees; Cell Survival; Dose-Response Relationship, Drug; Humans; Male; MCF-7 Cells; Melitten; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Staphylococcal Infections; Streptococcal Infections; Streptococcus; Survival Analysis

The In vitro activities of two antimicrobial cationic peptides, melittin and nisin alone and in combination with frequently used antibiotics (daptomycin, vancomycin, linezolid, ampicillin, and erythromycin), were assessed against clinical isolates of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Enterococcus faecalis. Using the broth microdilution method, minimum inhibitory concentration (MIC) ranges of melittin and nisin against all strains were 2-8 μg/ml and 2-32 μg/ml respectively. In combination studies performed with the microdilution checkerboard method using a fractional inhibitory concentration index of ≤ 0.5 as borderline, synergistic interactions occurred more frequently with nisin-ampicillin combination against MSSA and nisin-daptomycin combination against E. faecalis strains. The results of the time-killing curve analysis demonstrated that the concentration dependent rapid bactericidal activity of nisin, and that synergism or early synergism was detected in most strains when nisin or melittin was used in combination with antibiotics even at concentrations of 0.5 × MIC.

Topics: Anti-Bacterial Agents; Cells, Cultured; Drug Therapy, Combination; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Melitten; Methicillin-Resistant Staphylococcus aureus; Nisin; Staphylococcal Infections; Staphylococcus aureus

The in vitro activity of CA(1-7)M(2-9)NH(2), a 15-residue synthetic hybrid peptide derived from the sequences of cecropin A and melittin, alone and in combination with amoxicillin-clavulanate, imipenem, clarithromycin, ciprofloxacin, rifampin, and vancomycin, was investigated against 40 nosocomial isolates of methicillin-resistant Staphylococcus aureus. Antimicrobial activity of CA(1-7)M(2-9)NH(2) was measured by minimal inhibitory concentration, MBC, and time-kill studies. All isolates were inhibited at concentrations of 1 to 16 microg/mL. Combination studies performed with S. aureusATCC 43300 demonstrated synergy only when CA(1-7)M(2-9)NH(2) was combined with amoxicillin-clavulanate and imipenem. Our findings show that CA(1-7)M(2-9)NH(2) is active against methicillin-resistant S. aureusand that its activity is enhanced when it is combined with several antimicrobial agents.

Topics: Amoxicillin-Potassium Clavulanate Combination; Cross Infection; Drug Interactions; Female; Humans; Imipenem; Male; Melitten; Methicillin Resistance; Microbial Sensitivity Tests; Sensitivity and Specificity; Staphylococcal Infections; Staphylococcus aureus