Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens

Blanca Lorente-Torres, Jesús Llano-Verdeja, Pablo Castañera, Helena Á. Ferrero, Sergio Fernández-Martínez, Farzaneh Javadimarand, Luis M. Mateos, Michal Letek, Álvaro Mourenza
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Abstract

Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, bioinformatics, and systems biology, several existing drugs have been identified with potential efficacy against intracellular bacteria. For instance, neuroleptic agents like thioridazine and antipsychotic drugs such as chlorpromazine have shown effectiveness against Staphylococcus aureus and Listeria monocytogenes. Furthermore, anticancer drugs including tamoxifen and imatinib have been repurposed to induce autophagy and inhibit bacterial growth within host cells. Statins and anti-inflammatory drugs have also demonstrated the ability to enhance host immune responses against Mycobacterium tuberculosis. The review highlights the complex mechanisms these pathogens use to resist conventional treatments, showcases successful examples of drug repurposing, and discusses the methodologies used to identify and validate these drugs. Overall, drug repurposing offers a promising approach for developing new treatments for bacterial infections, addressing the urgent need for effective antimicrobial therapies.
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应对细胞内细菌病原体的药物再利用创新战略
由于细胞内细菌病原体能够逃避免疫防御和传统抗生素,因此给公共卫生带来了巨大挑战。最近,人们开始探索药物再利用的策略,以便为现有药物发现新的治疗用途,从而对抗这些感染。利用高通量筛选、生物信息学和系统生物学,已经发现了几种对细胞内细菌具有潜在疗效的现有药物。例如,硫利达嗪等神经抑制剂和氯丙嗪等抗精神病药物对金黄色葡萄球菌和单核细胞增生李斯特菌具有疗效。此外,包括他莫昔芬和伊马替尼在内的抗癌药物已被重新用于诱导自噬和抑制宿主细胞内的细菌生长。他汀类药物和抗炎药物也已证明能够增强宿主对结核分枝杆菌的免疫反应。综述强调了这些病原体抵抗常规治疗的复杂机制,展示了药物再利用的成功案例,并讨论了用于识别和验证这些药物的方法。总之,药物再利用为开发细菌感染的新疗法提供了一种前景广阔的方法,满足了对有效抗菌疗法的迫切需求。
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