According to the World Health Organization, infectious diseases, particularly those caused by multidrug-resistant bacteria (MDR), are projected to claim the lives of 15 million people by 2050. Septicemia carries a higher morbidity and mortality rate than infections caused by susceptible , and MDR-mediated ocular infections can lead to impaired vision and blindness. To identify and develop a potential drug against MDR , we employed reverse genetics-based target mining, drug prioritization, and evaluation. Rare Lipoprotein A (RlpA) was selected as the target protein, and its crystal structure was geometrically optimized. Molecular docking and virtual screening analyses revealed that RlpA exhibits strong binding affinity with 11 compounds. Among these, 3-chlorophthalic acid was evaluated, and subsequent assays demonstrated significant anti- activity with negligible cytotoxicity. The compound was further evaluated against both drug-susceptible and MDR strains , with cytotoxicity assessed using an MTT assay. The study demonstrated that 3-chlorophthalic acid exhibits potent anti- activity with minimal toxicity to host cells. Consequently, this compound emerges as a promising candidate against MDR , warranting further investigation.

中文翻译：

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作为多重耐药铜绿假单胞菌靶点的 RlpA 蛋白的鉴定、优先排序和评估


据世界卫生组织称，到 2050 年，传染病，特别是由多重耐药细菌 (MDR) 引起的传染病，预计将夺去 1500 万人的生命。败血症的发病率和死亡率高于易感细菌引起的感染，并且耐多药介导的眼部感染可导致视力受损和失明。为了识别和开发潜在的抗 MDR 药物，我们采用了基于反向遗传学的靶标挖掘、药物优先排序和评估。选择稀有脂蛋白A（RlpA）作为目标蛋白，对其晶体结构进行几何优化。分子对接和虚拟筛选分析表明，RlpA 与 11 种化合物表现出很强的结合亲和力。其中，对 3-氯邻苯二甲酸进行了评估，随后的测定显示出显着的抗活性和可忽略不计的细胞毒性。该化合物针对药物敏感菌株和 MDR 菌株进行了进一步评估，并使用 MTT 测定评估了细胞毒性。研究表明，3-氯邻苯二甲酸表现出有效的抗活性，对宿主细胞的毒性最小。因此，该化合物成为对抗 MDR 的有希望的候选药物，值得进一步研究。