Moncada-Diaz Maria Juliana, Rodríguez-Almonacid Cristian Camilo, Quiceno-Giraldo Eyson, Khuong Francis T H, Muskus Carlos, Karamysheva Zemfira N
Department of Cell Biology and Biochemistry, Texas Tech University Health Science Center, Lubbock, TX 79430, USA.
Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA.
Pathogens. 2024 Sep 27;13(10):835. doi: 10.3390/pathogens13100835.
The protozoan parasite causes leishmaniasis, a neglected tropical disease, that disproportionately affects underdeveloped countries. This disease has major health, economic, and social implications, particularly because of the limited treatment options, high cost, the severe side effects associated with available therapeutics, and the high rate of treatment failure caused by the parasites' growing resistance to current medications. In this review, we describe first the common strategies used by pathogens to develop drug resistance and then focus on the arsenal of available drugs to treat leishmaniasis, their modes of action, and the molecular mechanisms contributing to drug resistance in spp., including the role of genomic, transcriptional, and translational control. We focus more specifically on our recent discovery of translational reprogramming as a major driver of drug resistance leading to coordinated changes in the translation of transcripts and orchestrating changes in metabolome and lipidome to support drug resistance. A thorough understanding of these mechanisms is essential to identify the key elements needed to combat resistance and improve leishmaniasis treatment methods.
这种原生动物寄生虫会引发利什曼病，这是一种被忽视的热带疾病，对不发达国家的影响尤为严重。这种疾病对健康、经济和社会有着重大影响，特别是因为治疗选择有限、成本高昂、现有治疗方法存在严重副作用，以及寄生虫对当前药物的耐药性不断增强导致治疗失败率很高。在本综述中，我们首先描述病原体产生耐药性的常见策略，然后重点介绍治疗利什曼病的现有药物库、它们的作用方式，以及导致 种耐药性的分子机制，包括基因组、转录和翻译控制的作用。我们更具体地关注我们最近发现的翻译重编程是耐药性的主要驱动因素，它导致转录本翻译的协调变化，并协调代谢组和脂质组的变化以支持耐药性。深入了解这些机制对于确定对抗耐药性和改进利什曼病治疗方法所需的关键要素至关重要。
