Science：突破免疫的防线

　　

生物通报道：沙门氏菌是一种肠道菌，会引发肠胃炎和伤寒症等疾病。日前，伦敦帝国理工学院研究人员发表了一项新研究，揭示了沙门氏菌阻碍细胞防御机制的详细机制，文章发表在十一月十五日的Science杂志上。

将较小的细菌吞噬是细胞抵御感染的途径之一，随后细胞会用溶酶体中所含的毒性酶攻击病原菌。而Science杂志上的这项新研究显示，沙门氏菌的应对策略就是前赴后继将对自身有害的溶酶体酶耗尽。

溶酶体中杀菌的酶就像作战用的弹药，需要得到持续补充，这些酶通过精密的转运通路从细胞内的合成位点运入溶酶体。负责转运的蛋白在溶酶体将酶卸下后，就会返回合成工厂继续运送新酶。

伦敦帝国理工学院教授David Holden领导的研究团队发现，沙门氏菌能够通过特殊途径干扰溶酶体的酶补给系统。沙门氏菌在被吞噬后，临死前会释放蛋白来阻止转运蛋白在合成工厂与溶酶体间循环。

沙门氏菌在这场战役中，有效切断了溶酶体酶的补给线。随着沙门氏菌一波又一波的攻击，细胞中溶酶体的酶被耗空，从而丧失了杀菌能力。随后沙门氏菌就会掠夺这些被缴械的溶酶体。

Holden教授说，“这是沙门氏菌干扰宿主细胞防御机制的有效途径，它们就是这样将溶酶体重的资源收为己用。”

研究人员下一步会深入研究沙门氏菌蛋白起作用的分子机制，并在此基础上研发更有效的疫苗。这在当前非常重要，因为当前许多沙门氏菌都对抗生素产生了抗性。

沙门氏菌的不同菌株会引发肠胃炎、血液感染和伤寒症，每年沙门氏菌所造成的疾病和死亡有数百万。

（生物通编辑：叶予）

生物通推荐原文摘要：

Salmonella Inhibits Retrograde Trafficking of Mannose-6-Phosphate Receptors and Lysosome Function

Salmonella enterica is an intracellular bacterial pathogen that replicates within membrane-bound vacuoles through the action of effector proteins translocated into host cells. Salmonella vacuoles have characteristics of lysosomes but are reduced in hydrolytic enzymes transported by mannose-6-phosphate receptors (MPRs). We found that the effector SifA subverted Rab9-dependent retrograde trafficking of MPRs, thereby attenuating lysosome function. This required binding of SifA to its host cell target SKIP/PLEKHM2. Furthermore, SKIP regulated retrograde trafficking of MPRs in noninfected cells. Translocated SifA formed a stable complex with SKIP and Rab9 in infected cells. Sequestration of Rab9 by SifA-SKIP accounted for the effect of SifA on MPR transport and lysosome function. Growth of Salmonella increased in cells with reduced lysosomal activity and decreased in cells with higher lysosomal activity. These results suggest that Salmonella vacuoles undergo fusion with lysosomes whose potency has been reduced by SifA.