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Targeting the type III secretion system to treat bacterial infections

机译：靶向III型分泌系统以治疗细菌感染

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Introduction: Causative agents of pneumonia, gastroenteritis, typhoid fever, and plague all utilize a type III secretion system (T3SS) to directly inject proteins into human cells and cause disease. These bacterial pathogens are frequently resistant to antibiotics and novel treatment options are needed. The T3SS is essential for virulence and can be inhibited to prevent disease. Areas covered: T3SS structure and assembly are introduced in this review, highlighting targets for T3SS-specific therapeutics. Promising inhibitors of type III secretion (T3S), their modes of action, and successful techniques for their identification are reviewed. T3S inhibitor research has focused on small molecules identified in high-throughput screens, although recently inhibitors have also been identified or engineered by rational design. Promising compounds have emerged that inhibit T3S and attenuate virulence in several pathogens, including an engineered antibody in clinical trials. T3S inhibitor research may yield effective treatments and prophylactics that are effective against a wide range of human pathogens. Expert opinion: More techniques are needed to identify the mode of action for compounds identified in high-throughput screens, a long-standing challenge. Although only a few groups have attempted rational design of inhibitors, the approach has seen initial success and mechanistic follow-up studies are greatly simplified.
机译：简介：肺炎，肠胃炎，伤寒和鼠疫的病原体均利用III型分泌系统（T3SS）将蛋白质直接注入人体细胞并引起疾病。这些细菌病原体通常对抗生素具有抗性，因此需要新的治疗选择。 T3SS对于毒力至关重要，可以被抑制以预防疾病。涵盖的领域：本次综述介绍了T3SS的结构和组装，重点介绍了T3SS特定疗法的目标。审查了有希望的III型分泌（T3S）抑制剂，它们的作用方式以及用于鉴定的成功技术。 T3S抑制剂的研究集中在高通量筛选中鉴定出的小分子上，尽管最近抑制剂也已经通过合理的设计进行了鉴定或设计。已经出现了抑制T3S并减弱几种病原体中毒力的有前途的化合物，包括在临床试验中的工程抗体。 T3S抑制剂研究可能会产生有效的治疗方法和预防措施，可有效应对多种人类病原体。专家意见：需要更多技术来鉴定在高通量筛选中鉴定的化合物的作用方式，这是一项长期的挑战。尽管只有少数几组尝试合理设计抑制剂，但该方法已获得初步成功，并且大大简化了机理的后续研究。

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