Tachyplesin I (TPI) is a cationic β-hairpin antimicrobial peptide with broad-spectrum, potent antimicrobial activity. In this study, the all d-amino acid analogue of TPI (TPAD) was synthesized, and its structure and activity were determined. TPAD has comparable antibacterial activity to TPI on 14 bacterial strains, including four drug-resistant bacteria. Importantly, TPAD has significantly improved stability against enzymatic degradation and decreased hemolytic activity compared to TPI, indicating that it has better therapeutic potential. The induction of bacterial resistance using low concentrations of TPAD resulted in the activation of the QseC/B two-component system. Deletion of this system resulted in at least five-fold improvement of TPAD activity, and the combined use of TPAD with LED209, a QseC/B inhibitor, significantly enhanced the bactericidal effect against three classes of multidrug-resistant bacteria.

中文翻译：

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通过联合应用速激肽I和QseC / B信号通路抑制剂的类似物，增强了对耐多药细菌的活性。

速激肽I（TPI）是一种阳离子β-发夹式抗菌肽，具有广谱，有效的抗菌活性。在这项研究中，合成了TPI的所有d-氨基酸类似物（TPAD），并确定了其结构和活性。TPAD在14种细菌菌株（包括4种耐药细菌）上具有与TPI相当的抗菌活性。重要的是，与TPI相比，TPAD具有显着改善的抗酶促降解稳定性和降低的溶血活性，表明它具有更好的治疗潜力。使用低浓度的TPAD诱导细菌抗性导致QseC / B两组分系统活化。删除此系统后，TPAD活性至少提高了五倍，并且TPAD与QseC / B抑制剂LED209联合使用，