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首页> 外文OA文献 >Analogs of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the Parental Peptide
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Analogs of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the Parental Peptide

机译：蛙皮抗菌肽Temporin 1Tb的类似物表现出比亲本肽更宽的活性谱和更强的生物膜电位

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The frog skin-derived peptide Temporin 1Tb (TB) has gained increasing attention as novel antimicrobial agent for the treatment of antibiotic-resistant and/or biofilm-mediated infections. Nevertheless, such a peptide possesses a preferential spectrum of action against Gram-positive bacteria. In order to improve the therapeutic potential of TB, the present study evaluated the antibacterial and antibiofilm activities of two TB analogs against medically relevant bacterial species. Of the two analogs, TB_KKG6A has been previously described in the literature, while TB_L1FK is a new analog\uddesigned by us through statistical-based computational strategies. Both TB analogs displayed a faster and stronger bactericidal activity than the parental peptide, especially against Gram-negative bacteria in planktonic form. Differently from the parental peptide, TB_KKG6A and TB_L1FK were able to inhibit the formation of Staphylococcus aureus biofilms by more than 50% at 12 μM, while only TB_KKG6A prevented the formation of Pseudomonas aeruginosa biofilms at 24 μM. A marked antibiofilm activity against preformed biofilms of both bacterial species was observed for the two TB analog when used in combination with EDTA. Analysis of synergism at the cellular level suggested that the antibiofilm activity exerted by the peptide-EDTA combinations against mature\udbiofilms might be due mainly to a disaggregating effect on the extracellular matrix in the case of S. aureus, and to a direct activity on biofilm-embedded cells in the case of P. aeruginosa. Both analogs displayed a low hemolytic effect at the active concentrations and, overall, TB_L1FK resulted less cytotoxic toward mammalian cells. Collectively, the results obtained demonstrated that subtle changes in the primary sequence of TB may provide TB analogs that, used alone or in combination with adjuvant molecules such as EDTA, exhibit promising features against both planktonic and biofilm cells of medically relevant bacteria.
机译：青蛙皮肤来源的肽Temporin 1Tb（TB）作为用于治疗抗生素耐药性和/或生物膜介导的感染的新型抗菌剂，受到越来越多的关注。然而，这种肽具有针对革兰氏阳性细菌的优先作用谱。为了提高结核病的治疗潜力，本研究评估了两种结核病类似物对医学相关细菌物种的抗菌和生物膜活性。在这两个类似物中，TB_KKG6A先前已在文献中进行了描述，而TB_L1FK是我们通过基于统计的计算策略设计的新类似物。两种TB类似物都比亲本肽显示出更快，更强的杀菌活性，尤其是对浮游形式的革兰氏阴性菌。与亲本肽不同，TB_KKG6A和TB_L1FK在12μM时能抑制金黄色葡萄球菌生物膜的形成超过50％，而只有TB_KKG6A在24μM时能阻止铜绿假单胞菌生物膜的形成。当与EDTA组合使用时，两个TB类似物均观察到针对两种细菌的​​预先形成的生物膜的显着抗生物膜活性。在细胞水平上的协同作用分析表明，肽-EDTA组合对成熟\ udbiofilm膜产生的抗生物膜活性可能主要是由于金黄色葡萄球菌对细胞外基质的分解作用，以及对生物膜的直接活性在铜绿假单胞菌的情况下被包埋。两种类似物在活性浓度下均表现出低溶血作用，总体而言，TB_L1FK对哺乳动物细胞的细胞毒性较小。总体而言，获得的结果表明，结核病一级序列的细微变化可能提供了单独或与佐剂分子（如EDTA）结合使用的结核病类似物，具有针对医学相关细菌的浮游和生物膜细胞的有希望的特征。

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