Hirakawa Hidetada, Suzue Kazutomo, Tomita Haruyoshi
Department of Bacteriology, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, Japan.
Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, Japan.
Vaccines (Basel). 2022 Mar 10;10(3):422. doi: 10.3390/vaccines10030422.
The Tol/Pal system (also written as "The Tol-Pal system") is a set of protein complexes produced by most Gram-negative bacteria. It comprises the inner membrane-associated and the outer membrane-anchored subunits composed of the TolA, TolQ, and TolR proteins and the TolB and Pal proteins, respectively. Although the Tol/Pal system was first defined as bacterial proteins involved in colicin uptake of , its global roles have been characterized in several studies as mentioned in this article. Pathogenesis of many Gram-negative pathogens is sustained by the Tol/Pal system. It is also essential for cell growth and fitness in some pathogens. Therefore, the Tol/Pal system is proposed as a potential target for antimicrobial chemotherapy. Although the / mutants are low in virulence, they still have the ability to stimulate the immune system. The Pal protein is highly immunogenic and induces both adaptive and innate immune responses. Therefore, the / mutant strains and Pal proteins also have potential vaccine properties. For these reasons, the Tol/Pal system represents a promising research target in the development of antibacterial therapeutic strategies for refractory infections caused by multi-drug-resistant (MDR), Gram-negative pathogens. In this paper, we summarize studies on the Tol/Pal system associated with bacterial pathogenesis and vaccine development.
Tol/Pal系统（也写作“The Tol-Pal system”）是大多数革兰氏阴性菌产生的一组蛋白质复合物。它分别由与内膜相关的和锚定在外膜的亚基组成，内膜相关亚基由TolA、TolQ和TolR蛋白组成，外膜锚定亚基由TolB和Pal蛋白组成。尽管Tol/Pal系统最初被定义为参与大肠杆菌素摄取的细菌蛋白，但如本文所述，其在多项研究中已被明确了整体作用。许多革兰氏阴性病原体的致病过程由Tol/Pal系统维持。在一些病原体中，它对细胞生长和适应性也至关重要。因此，Tol/Pal系统被提议作为抗微生物化疗的潜在靶点。尽管/突变体的毒力较低，但它们仍有刺激免疫系统的能力。Pal蛋白具有高度免疫原性，可诱导适应性免疫反应和先天性免疫反应。因此，/突变株和Pal蛋白也具有潜在的疫苗特性。基于这些原因，Tol/Pal系统是开发针对耐多药（MDR）革兰氏阴性病原体引起的难治性感染的抗菌治疗策略的一个有前景的研究靶点。在本文中，我们总结了与细菌致病机制和疫苗开发相关的Tol/Pal系统的研究。
