A prolonged therapy, primarily responsible for development of drug resistance by Mycobacterium tuberculosis (Mtb), obligates any new TB regimen to not only reduce treatment duration but also escape pathogen resistance mechanisms. With the aim of harnessing the host response in providing support to existing regimens, we used sertraline (SRT) to stunt the pro-pathogenic type I IFN response of macrophages to infection. While SRT alone could only arrest bacterial growth, it effectively escalated the bactericidal activities of Isoniazid (H) and Rifampicin (R) in macrophages. This strengthening of antibiotic potencies by SRT was more evident in conditions of ineffective control by these frontline TB drug, against tolerant strains or dormant Mtb. SRT, could significantly combine with standard TB drugs to enhance early pathogen clearance from tissues of mice infected with either drug sensitive/ tolerant strains of Mtb. Further, we demonstrate an enhanced protection in acute TB infection of the highly susceptible C3HeB/FeJ mice with the combination therapy signifying the use of SRT as a potent adjunct to standard TB therapeutic regimens against bacterial populations of diverse physiology. This study advocates a novel host directed adjunct therapy regimen for TB with a clinically approved anti-depressant to achieve quicker and greater control of infection.

中文翻译：

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抗抑郁药舍曲林提供了一种新型的针对宿主的治疗模块，可增强结核病治疗

延长治疗时间主要负责结核分枝杆菌（Mtb）的耐药性发展，这使得任何新的TB方案都必须缩短治疗时间，并避免病原体耐药机制。为了利用宿主反应为现有方案提供支持，我们使用了舍曲林（SRT）来抑制巨噬细胞对感染的促病原性I型IFN反应。虽然单独使用SRT只能阻止细菌生长，但它可以有效地提高巨噬细胞中异烟肼（H）和利福平（R）的杀菌活性。在这些一线结核病药物无法有效控制耐药菌株或休眠Mtb的情况下，通过SRT增强抗生素效力更为明显。SRT，可以与标准TB药物显着结合，以提高感染了Mtb药物敏感/耐受菌株的小鼠组织的早期病原体清除率。此外，我们证明了联合疗法表明对高度易感的C3HeB / FeJ小鼠的急性TB感染具有增强的保护作用，这表明联合使用SRT作为针对多种生理细菌种群的标准TB治疗方案的有效辅助手段。这项研究提倡一种新型的针对宿主的结核病宿主定向辅助治疗方案，该方案应采用临床认可的抗抑郁药，以更快，更好地控制感染。我们证明了联合疗法表明对高度易感的C3HeB / FeJ小鼠的急性TB感染具有增强的保护作用，这表明联合使用SRT作为针对不同生理细菌种群的标准TB治疗方案的有效辅助手段。这项研究提倡一种针对结核病的新型宿主定向辅助治疗方案，该方案应采用临床认可的抗抑郁药，以更快，更好地控制感染。我们证明了联合疗法表明对高度易感的C3HeB / FeJ小鼠的急性TB感染具有增强的保护作用，这表明联合使用SRT作为针对不同生理细菌种群的标准TB治疗方案的有效辅助手段。这项研究提倡一种针对结核病的新型宿主定向辅助治疗方案，该方案应使用经过临床批准的抗抑郁药，以更快，更好地控制感染。