Introduction

In 2018, an estimated 377,000 people developed multidrug-resistant tuberculosis (MDR-TB), urging for new effective treatments. In the last years, it has been accepted that efflux pumps play an important role in the evolution of drug resistance. Strategies are required to mitigate the consequences of the activity of efflux pumps.

Areas covered

Based upon the literature available in PubMed, up to February 2020, on the diversity of efflux pumps in Mycobacterium tuberculosis and their association with drug resistance, studies that identified efflux inhibitors and their effect on restoring the activity of antimicrobials subjected to efflux are reviewed. These support a new strategy for the development of anti-TB drugs, including efflux inhibitors, using in silico drug repurposing.

Expert opinion

The current literature highlights the contribution of efflux pumps in drug resistance in M. tuberculosis and that efflux inhibitors may help to ensure the effectiveness of anti-TB drugs. However, despite the usefulness of efflux inhibitors in in vitro studies, in most cases their application in vivo is restricted due to toxicity. In a time when new drugs are needed to fight MDR-TB and extensively drug-resistant TB, cost-effective strategies to identify safer efflux inhibitors should be implemented in drug discovery programs.

中文翻译：

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外排泵抑制剂是一种抗药性结核的有前途的辅助疗法：一种重新评估分枝杆菌靶标和重新利用旧药物的新策略。

介绍

2018年，估计有37.7万人患上了耐多药结核病（MDR-TB），并呼吁采取新的有效疗法。在过去的几年中，外排泵在耐药性的发展中起着重要的作用，这一点已为人们所接受。需要采取策略来减轻外排泵活动的后果。

覆盖区域

基于截至2020年2月PubMed上可获得的文献，关于结核分枝杆菌外排泵的多样性及其与耐药性的关系，对鉴定外排抑制剂及其对恢复外排抗菌素活性的作用的研究进行了综述。这些支持使用计算机模拟药物的新用途开发抗结核病药物（包括外排抑制剂）的新策略。

专家意见

当前文献突出了外排泵对结核分枝杆菌耐药性的贡献，外排抑制剂可能有助于确保抗结核药物的有效性。然而，尽管外排抑制剂在体外研究中有用，但是在大多数情况下，由于毒性，它们在体内的应用受到限制。在需要新药抗击耐多药结核和广泛耐药结核的时代，在药物发现计划中应采用经济有效的策略来鉴定更安全的外排抑制剂。