Institute of Veterinary Bacteriology, University of Bern, Laenggasstrasse 122, CH-3012 Bern, Switzerland.
Vet Microbiol. 2011 Nov 21;153(1-2):51-8. doi: 10.1016/j.vetmic.2011.05.018. Epub 2011 May 19.
RTX toxins are bacterial pore-forming toxins that are particularly abundant among pathogenic species of Pasteurellaceae, in which they play a major role in virulence. RTX toxins of several primary pathogens of the family of Pasteurellaceae are directly involved in causing necrotic lesions in the target organs. Many RTX toxins are known as haemolysins because they lyse erythrocytes in vitro, an effect that is non-specific, but which serves as a useful marker in bacteriological identification and as an easily measurable signal in vitro in experimental studies. More recent studies have shown that the specific targets of most RTX toxins are leukocytes, with RTX toxins binding to the corresponding β-subunit (CD18) of β2 integrins and then exerting cytotoxic activity. After uptake by the target cell, at sub-lytic concentrations, some RTX toxins are transported to mitochondria and induce apoptosis. For several RTX toxins the binding to CD18 has been shown to be host specific and this seems to be the basis for the host range specificity of these RTX toxins. Observations on two very closely related species of the Pasteurellaceae family, Actinobacillus suis, a porcine pathogen particularly affecting suckling pigs, and Actinobacillus equuli subsp. haemolytica, which causes pyosepticaemia in new-born foals (sleepy foal disease), have revealed that they express different RTX toxins, named ApxI/II and Aqx, respectively. These RTX toxins are specifically cytotoxic for porcine and equine leukocytes, respectively. Furthermore, the ApxI and Aqx toxins of these species, when expressed in an isogenetic background in Escherichia coli, are specifically cytotoxic for leukocytes of their respective hosts. These data indicate the determinative role of RTX toxins in host specificity of pathogenic species of Pasteurellaceae.
RTX 毒素是一种细菌形成孔的毒素,在巴斯德氏菌科的致病种中特别丰富,在这些种中,它们在毒力中起主要作用。巴斯德氏菌科的几种主要病原体的 RTX 毒素直接参与引起靶器官的坏死病变。许多 RTX 毒素被称为溶血素,因为它们在体外裂解红细胞,这种作用是非特异性的,但作为细菌学鉴定中的有用标记物,并且作为实验研究中体外可测量的信号。最近的研究表明,大多数 RTX 毒素的特定靶标是白细胞,RTX 毒素与相应的 β2 整合素的 β 亚基(CD18)结合,然后发挥细胞毒性作用。在靶细胞摄取后,在亚裂解浓度下,一些 RTX 毒素被转运到线粒体并诱导细胞凋亡。对于几种 RTX 毒素,已经表明与 CD18 的结合是宿主特异性的,这似乎是这些 RTX 毒素宿主范围特异性的基础。对巴斯德氏菌科的两个非常密切相关的种,即猪病原体特别影响仔猪的猪放线杆菌和引起新生驹(昏睡驹病)败血病的马放线杆菌亚种溶血,的观察表明,它们表达不同的 RTX 毒素,分别命名为 ApxI/II 和 Aqx。这些 RTX 毒素分别对猪和马的白细胞具有特异性细胞毒性。此外,这些种的 ApxI 和 Aqx 毒素在大肠杆菌中的同基因背景中表达时,对各自宿主的白细胞具有特异性细胞毒性。这些数据表明 RTX 毒素在巴斯德氏菌科的致病种的宿主特异性中起决定性作用。