Pseudomonas aeruginosa is one of the leading antibiotic-resistant gram-negative organisms responsible for nosocomial infections. Multidrug pathogen resistance leads to the low antibiotic therapy efficiency. The solution for this problem involves developing new therapeutic agents that operate under different principles to the currently available antibiotics. The Type Three Secretion System (T3SS) is a major virulence factor in Pseudomonas aeruginosa. This review presents a brief description of structure and regulation of T3SS, which has been shown to contribute to the virulence of Gram-negative bacteria with different types of parasitism and is extremely necessary for the manifestation of the pathogenesis of diseases caused by them. The secretion apparatus is formed after bacteria contact with eukaryotic cell and allows the bacterium to inject toxins directly into the host cell cytoplasm. The T3SS regulation is a strictly hierarchically organized process that occurs at least at two levels, transcriptional and secretory. Thus, T3SS appears to be a highly attractive target for innovative therapies as it possesses a number of advantages over antibiotics: T3SS inhibitors are expected to have a lower risk of selecting resistance because they do not suppress the viability of pathogens, but only reduce bacterial virulence; inhibitors will be effective regardless of acquired antibiotic resistance; inhibitors will not to exert negligible effects on commensal bacteria. To date, a number of T3SS inhibitors with various nature and different mechanism of action have been identified. The discovered inhibitors suppress the transcription of the T3SS genes, toxins translocation and inhibit the effector molecules. For many of the developed inhibitors, their specific activity was shown in in vitro experiments, for few of them the antibacterial effect was shown in animal models and only two inhibitors are ongoing to test in clinical trials now: the Ftortiazinon and the antibodies MEDI3902.

中文翻译：

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铜绿假单胞菌的三型分泌系统作为抗毒药物开发的靶点

铜绿假单胞菌是导致医院感染的主要耐药革兰氏阴性菌之一。多药病原体耐药导致抗生素治疗效率低。该问题的解决方案涉及开发新的治疗剂，其作用原理与目前可用的抗生素不同。三型分泌系统 (T3SS) 是铜绿假单胞菌的主要毒力因子。这篇综述简要描述了 T3SS 的结构和调控，它已被证明有助于具有不同寄生类型的革兰氏阴性菌的毒力，并且对于由它们引起的疾病的发病机制的表现是非常必要的。分泌器是细菌与真核细胞接触后形成的，它允许细菌将毒素直接注入宿主细胞的细胞质中。T3SS 调节是一个严格按等级组织的过程，至少发生在转录和分泌两个层面。因此，T3SS 似乎是创新疗法的一个极具吸引力的目标，因为它具有许多优于抗生素的优势：预计 T3SS 抑制剂选择耐药性的风险较低，因为它们不会抑制病原体的生存能力，而只会降低细菌毒力; 无论获得性抗生素耐药性如何，抑制剂都将有效；抑制剂不会对共生细菌产生微不足道的影响。迄今为止，已经确定了许多具有不同性质和不同作用机制的 T3SS 抑制剂。发现的抑制剂抑制 T3SS 基因的转录、毒素易位并抑制效应分子。对于许多开发的抑制剂，它们的特定活性在体外实验中得到了证明，其中很少有在动物模型中显示出抗菌作用，现在只有两种抑制剂正在进行临床试验：Ftortiazinon 和抗体 MEDI3902。