A new antibacterial drug is urgently needed. We employed a protein–DNA complex-guided pharmacophore modeling approach to screen inhibitors against the response regulator PmrA of polymyxin B-resistant Klebsiella pneumoniae (KP). The identified lead, E1 (IC₅₀ = 10.2 μM), targeted the DNA-binding domain of PmrA (K_D = 1.7 μM), whose conserved residues R171, R198, K203, and Y214 have been shown to be hotspots for antimicrobial development. Treatment of E1 restored the susceptibility of KP to polymyxin B.

中文翻译：

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以蛋白质-DNA复合物为指导的抗菌肽E1的发现，其通过靶向反应调节物PmrA来恢复肺炎克雷伯菌对多粘菌素B的敏感性†

迫切需要一种新的抗菌药物。我们采用了蛋白质-DNA复合物指导的药效团建模方法来筛选针对多粘菌素B耐药肺炎克雷伯菌肺炎克雷伯氏菌（KP）的应答调节因子PmrA的抑制剂。鉴定出的铅E1（IC ₅₀ = 10.2μM）靶向PmrA的DNA结合域（K _D = 1.7μM），其保守残基R171，R198，K203和Y214已被证明是抗菌发展的热点。E1的治疗恢复了KP对多粘菌素B的敏感性。