Lesnick M L, Reiner N E, Fierer J, Guiney D G
Department of Medicine 0640, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Mol Microbiol. 2001 Mar;39(6):1464-70. doi: 10.1046/j.1365-2958.2001.02360.x.
ADP-ribosylating enzymes, such as cholera and diphtheria toxins, are key virulence factors for a variety of extracellular bacterial pathogens but have not been implicated previously during intracellular pathogenesis. Salmonella strains are capable of invading epithelial cells and localizing in macrophages during infection. The spvB virulence gene of Salmonella is required for human macrophage cytotoxicity in vitro and for enhancing intracellular bacterial proliferation during infection. Here, we present evidence that spvB encodes an ADP-ribosylating enzyme that uses actin as a substrate and depolymerizes actin filaments when expressed in CHO cells. Furthermore, site-directed mutagenesis demonstrates that the ADP-ribosylating activity of SpvB is essential for Salmonella virulence in mice. As spvB is expressed by Salmonella strains after invasion of epithelial cells or phagocytosis by macrophages, these results suggest that SpvB functions as an intracellular ADP-ribosylating toxin critical for the pathogenesis of Salmonella infections.
ADP核糖基化酶，如霍乱毒素和白喉毒素，是多种细胞外细菌病原体的关键毒力因子，但此前尚未发现其在细胞内致病过程中发挥作用。沙门氏菌菌株在感染过程中能够侵入上皮细胞并定位于巨噬细胞内。沙门氏菌的spvB毒力基因在体外对人巨噬细胞具有细胞毒性，并在感染过程中增强细胞内细菌的增殖。在此，我们提供证据表明，spvB编码一种ADP核糖基化酶，该酶以肌动蛋白为底物，在CHO细胞中表达时可使肌动蛋白丝解聚。此外，定点诱变表明，SpvB的ADP核糖基化活性对小鼠体内沙门氏菌的毒力至关重要。由于spvB在沙门氏菌菌株侵入上皮细胞或被巨噬细胞吞噬后表达，这些结果表明，SpvB作为一种细胞内ADP核糖基化毒素，对沙门氏菌感染的发病机制至关重要。
