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.
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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DOI：
10.3389/fchem.2017.00024
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发表时间：
2017
影响因子：
5.5
通讯作者：
Batoni G
中科院分区：
文献类型：
--
作者：
Grassi L;Maisetta G;Maccari G;Esin S;Batoni G
蛙皮衍生肽 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而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种类的抗菌和抗生物膜活性。在这两种类似物中，TB_KKG6A先前已在文献中描述过，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 类似物均表现出比亲本肽更快更强的杀菌活性，特别是针对浮游形式的革兰氏阴性菌。与亲本肽不同，TB_KKG6A 和 TB_L1FK 在 12 μM 时能够抑制金黄色葡萄球菌生物膜的形成超过 50%，而只有 TB_KKG6A 在 24 μM 时能够阻止铜绿假单胞菌生物膜的形成。当与 EDTA 组合使用时，观察到两种 TB 类似物对两种细菌物种的预形成生物膜具有显着的抗生物膜活性。细胞水平的协同分析表明，肽-EDTA组合对成熟生物膜发挥的抗生物膜活性可能主要是由于在金黄色葡萄球菌的情况下对细胞外基质的解聚作用，以及在铜绿假单胞菌的情况下对生物膜嵌入细胞的直接活性。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。总的来说，获得的结果表明，TB 一级序列的细微变化可能会提供 TB 类似物，单独使用或与 EDTA 等佐剂分子组合使用，对医学相关细菌的浮游细胞和生物膜细胞都表现出有希望的特性。
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 designed 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 analogs 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 biofilms 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.