Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Toxins (Basel). 2019 Dec 10;11(12):720. doi: 10.3390/toxins11120720.
The repeats-in-toxin (RTX) family represents a unique class of bacterial exoproteins. The first family members described were toxins from Gram-negative bacterial pathogens; however, additional members included exoproteins with diverse functions. Our review focuses on well-characterized RTX family toxins from (LtxA), (LktA), (CyaA), uropathogenic (HlyA), and (ApxIIIA), as well as the studies that have honed in on a single host cell receptor for RTX toxin interactions, the β integrins. The β integrin family is composed of heterodimeric members with four unique alpha subunits and a single beta subunit. β integrins are only found on leukocytes, including neutrophils and monocytes, the first responders to inflammation following bacterial infection. The LtxA, LktA, HlyA, and ApxIIIA toxins target the shared beta subunit, thereby targeting all types of leukocytes. Specific β integrin family domains are required for the RTX toxin's cytotoxic activity and are summarized here. Research examining the domains of the RTX toxins required for cytotoxic and hemolytic activity is also summarized. RTX toxins attack and kill phagocytic immune cells expressing a single integrin family, providing an obvious advantage to the pathogen. The critical question that remains, can the specificity of the RTX-β integrin interaction be therapeutically targeted?
RTX 家族代表了一类独特的细菌外分泌蛋白。最初描述的家族成员是革兰氏阴性细菌病原体的毒素；然而，其他成员还包括具有多种功能的外分泌蛋白。我们的综述重点介绍了来自 （LtxA）、 （LktA）、 （CyaA）、尿路致病性 （HlyA）和 （ApxIIIA）的特征良好的 RTX 家族毒素，以及针对 RTX 毒素相互作用的单个宿主细胞受体的研究，即 β 整合素。β 整合素家族由具有四个独特的 α 亚基和一个单一的 β 亚基的异二聚体成员组成。β 整合素仅存在于白细胞上，包括中性粒细胞和单核细胞，这是细菌感染后炎症的第一反应者。LtxA、LktA、HlyA 和 ApxIIIA 毒素针对共同的 β 亚基，从而针对所有类型的白细胞。RTX 毒素的细胞毒性活性所需的特定 β 整合素家族结构域在这里进行了总结。还总结了研究 RTX 毒素细胞毒性和溶血活性所需的结构域。RTX 毒素攻击和杀死表达单个整合素家族的吞噬免疫细胞，这为病原体提供了明显的优势。仍然存在的关键问题是，RTX-β 整合素相互作用的特异性能否成为治疗靶点？
