چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| لیلا رهبرنیا | اول |
| سمیه نبی زاده | دوم |
| عنوان | متن |
|---|---|
| خلاصه مقاله | Abstract Introduction: Lasioglossin-III (LL-III) peptide isolated from the eusocial bee Lasioglossum laticeps venom is known for a wide range of antimicrobial effect against bacteria coupled with low hemolytic action. However, some modifications can raise its therapeutic potential. In this study, we aimed to design a hybrid peptide including LL-III and Melittin analog to extend antimicrobial abilities and reduce toxicity to healthy cells. Methods: In the present study, a hybrid peptide with modified properties was designed via computational tools. Molecular dynamic (MD) and coarse-grained (CG) simulations were done to evaluate the stability and interaction of the hybrid peptide with related membrane models. The antimicrobial properties of the designed peptide were determined by MIC and MBC methods. Blood hemolysis test and MTT assay were used to evaluate the toxicity of the designed peptide. The effect of the designed peptide on biofilm formation was examined by biofilm forming assay, and scanning electron microscopy. Results: In this study, a truncated Melittin peptide (11 amino acids) was fused to an LL-III peptide (15 amino acids) to raise the antimicrobial activity. A new hybrid peptide analog (LM1) was selected by replacing the arginine with isoleucine in the fifth position of truncated Melittin to raise the antimicrobial rate of the peptide. The potential for binding of the LM1 to lipid membrane (D factor) was increased from 2.02 related to Melittin to 3.62. The RMSD of the LM1 peptide was in the range of 0.2 to 0.8, which, after 160 ns, reached stability. RMSD and RMSF results indicated no unwanted fluctuations during the 200 ns MD simulation. A significant movement of LM1 peptide inside the S. aureus membrane(4.76nm) and A. baumanni membrane (3.2nm) was observed by CG simulation. The MIC and MBC values for the LM1 peptide were calculated in a range of 3.125–12.5 μg/ml. Based on MTT assay results, LM1 peptide indicated less toxicity than natural MLT. The hemolytic activity of the LM1 analog was equal to 16 μg/mL concentration. Based on the results of the hemolysis test, a concentration of 125.3 μg/mL of peptide, which is equal to the reported MIC for A. baumannii led to 25% hemolysis of the blood, and a concentration of 25.6 μg/mL of peptide, which is equal to the MIC of S. aureus led to 37.5% hemolysis of the blood. At last, the scanning electron microscope (SEM) images of S. aureus and A. baumannii treated by LM1 demonstrated that LM1 had a significant effect on inhibiting biofilm formation. Based on the results, a concentration of 6.25 μg/ml of peptide inhibited biofilm formation by 41.6%. Also, a concentration of 3.125 μg/ml of peptide inhibited biofilm formation by 41.6%. Discussion: Our findings highlight high stability, anti-microbial and anti-biofilm ability of the LM1 peptide. LM1 peptide could be a new therapeutic candidate for inhibiting the growth of A. baumannii and S. aureus bacteria. |
| کلمات کلیدی | anti-Biofilm formation; Melittin; Lasioglossin; anti-microbial activity; MD simulation |
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