Department of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Science. 2012 Nov 16;338(6109):960-3. doi: 10.1126/science.1229224.
Unlike other Salmonellae, the intracellular bacterial human pathogen Salmonella Typhi exhibits strict host specificity. The molecular bases for this restriction are unknown. Here we found that the expression of a single type III secretion system effector protein from broad-host Salmonella Typhimurium allowed Salmonella Typhi to survive and replicate within macrophages and tissues from mice, a nonpermissive host. This effector proteolytically targeted Rab32, which controls traffic to lysosome-related organelles in conjunction with components of the biogenesis of lysosome-related organelle complexes (BLOCs). RNA interference-mediated depletion of Rab32 or of an essential component of a BLOC complex was sufficient to allow S. Typhi to survive within mouse macrophages. Furthermore, S. Typhi was able to survive in macrophages from mice defective in BLOC components.
与其他沙门氏菌不同，细胞内细菌病原体伤寒沙门氏菌表现出严格的宿主特异性。这种限制的分子基础尚不清楚。在这里，我们发现来自广谱宿主沙门氏菌鼠伤寒的单个 III 型分泌系统效应蛋白的表达使伤寒沙门氏菌能够在非允许宿主的巨噬细胞和组织中存活和复制。这种效应蛋白对 Rab32 进行蛋白水解靶向，Rab32 与溶酶体相关细胞器生物发生复合物 (BLOC) 的成分一起控制到溶酶体相关细胞器的运输。RNA 干扰介导的 Rab32 或 BLOC 复合物的必需成分的耗尽足以使 S. Typhi 在小鼠巨噬细胞中存活。此外，S. Typhi 能够在 BLOC 成分缺陷的小鼠巨噬细胞中存活。
