Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
EMBO Rep. 2013 Jan;14(1):95-102. doi: 10.1038/embor.2012.186. Epub 2012 Nov 23.
Unlike other Salmonella, which can infect a broad range of hosts causing self-limiting infection, Salmonella Typhi is an exclusively human pathogen that causes typhoid fever, a life-threatening systemic disease. Typhoid toxin is a unique virulence factor of Salmonella Typhi, which is expressed when the bacteria are within mammalian cells. Here, we report that an N-acetyl-β-D-muramidase similar to phage endolysins encoded within the same pathogenicity islet as the toxin is required for typhoid toxin secretion. Genetic and functional analysis of TtsA revealed unique amino acids at its predicted peptidoglycan-binding domain that are essential for protein secretion and that distinguishes this protein from other homologues. We propose that TtsA defines a new protein secretion mechanism recently evolved from the machine that mediates phage release.
与其他可感染广泛宿主并导致自限性感染的沙门氏菌不同,伤寒沙门氏菌是一种专门的人类病原体,可引起伤寒,这是一种危及生命的全身性疾病。伤寒毒素是伤寒沙门氏菌的一种独特毒力因子,只有当细菌在哺乳动物细胞内时才会表达。在这里,我们报告称,与毒素在同一致病性岛内编码的噬菌体内切酶相似的 N-乙酰-β-D-胞壁酰基酰胺酶对于伤寒毒素的分泌是必需的。对 TtsA 的遗传和功能分析表明,其预测的肽聚糖结合结构域存在独特的氨基酸,这些氨基酸对于蛋白质分泌是必需的,并且将该蛋白与其他同源物区分开来。我们提出 TtsA 定义了一种新的蛋白质分泌机制,该机制是最近从介导噬菌体释放的机器进化而来的。