Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, Prague, Czech Republic.
Curr Opin Infect Dis. 2021 Jun 1;34(3):187-196. doi: 10.1097/QCO.0000000000000726.
RTX toxin action often defines the outcome of bacterial infections. Here, we discuss the progress in understanding the impacts of RTX toxin activities on host immunity.
Bordetella pertussis CyaA activity paralyzes sentinel phagocytic cells by elevating cellular cAMP levels and blocks differentiation of infiltrating monocytes into bactericidal macrophages, promoting also de-differentiation of resident alveolar macrophages into monocyte-like cells. Vibrio cholerae multifunctional autoprocessing repeats-in-toxins (MARTX), through Rho inactivating and α/β-hydrolase (ABH) domain action blocks mitogen-activated protein kinase signaling in epithelial cells and dampens the inflammatory responses of intestinal epithelia by blocking immune cell recruitment. The action of actin crosslinking effector domain and Ras/Rap1-specific endopeptidase (RRSP) domains of MARTX compromises the phagocytic ability of macrophages. Aggregatibacter actinomycetemcomitans LtxA action triggers neutrophil elastase release into periodontal tissue, compromising the epithelial barrier and promoting bacterial spreads into deeper tissue.
Action of RTX toxins enables bacterial pathogens to cope with the fierce host immune defenses. RTX toxins often block phagocytosis and bactericidal reactive oxygen species and NO production. Some RTX toxins can reprogram the macrophages to less bactericidal cell types. Autophagy is hijacked for example by the activity of the V. cholerae ABH effector domain of the MARTX protein. Subversion of immune functions by RTX toxins thus promotes bacterial survival and proliferation in the host.
RTX 毒素的作用常常决定了细菌感染的结果。在这里，我们讨论了对 RTX 毒素活性对宿主免疫影响的理解进展。
百日咳博德特氏菌 CyaA 通过提高细胞 cAMP 水平使感应吞噬细胞瘫痪，并阻止浸润的单核细胞分化为杀菌性巨噬细胞，同时促进驻留肺泡巨噬细胞向单核细胞样细胞去分化。霍乱弧菌多功能自加工重复内毒素（MARTX）通过 Rho 失活和 α/β-水解酶（ABH）结构域作用阻断上皮细胞中丝裂原激活的蛋白激酶信号转导，并通过阻断免疫细胞募集来抑制肠道上皮的炎症反应。MARTX 的肌动蛋白交联效应结构域和 Ras/Rap1 特异性内肽酶（RRSP）结构域的作用损害了巨噬细胞的吞噬能力。伴放线放线杆菌 LtxA 作用引发中性粒细胞弹性蛋白酶释放到牙周组织中，破坏上皮屏障并促进细菌向更深层组织扩散。
RTX 毒素的作用使细菌病原体能够应对宿主强烈的免疫防御。RTX 毒素通常阻断吞噬作用和杀菌性活性氧物质和 NO 的产生。一些 RTX 毒素可以将巨噬细胞重新编程为杀菌能力较低的细胞类型。例如，V. cholerae ABH 效应结构域的活性劫持了自噬。因此，RTX 毒素对免疫功能的颠覆促进了细菌在宿主中的存活和增殖。
