The ATP-dependent Lon protease of Salmonella enterica serovar Typhimurium regulates invasion and expression of genes carried on Salmonella pathogenicity island 1
The ATP-dependent Lon protease of Salmonella enterica serovar Typhimurium regulates invasion and expression of genes carried on Salmonella pathogenicity island 1
复制标题
DOI：
10.1128/jb.184.1.224-232.2002
复制
发表时间：
2002-01-01
影响因子：
3.2
通讯作者：
Yamamoto, T
中科院分区：
文献类型：
--
作者：
Takaya, A;Tomoyasu, T;Yamamoto, T
鼠伤寒沙门氏菌感染发病机制的早期步骤是细菌渗透肠上皮。渗透需要沙门氏菌致病岛1（SPIT）中发现的入侵基因的表达。这些基因以复杂的方式由SPIT中的调控因子（包括HilA和InvF）和SPIT外的调控因子（如双组分调控系统和小DNA结合蛋白）控制。我们在此报道了S.肠血清型鼠伤寒沙门氏菌受ATP依赖性Lon蛋白酶的负调控，已知Lon蛋白酶是大肠杆菌中蛋白水解的主要贡献者。一个被破坏的突变体的ton能够有效地侵入培养的上皮细胞，并显示出增加的生产和分泌的三个确定的SPIT蛋白，SipA，SipC，和SipD。Ion突变体还显示SPIT基因hilA、invF、sipA和sipC的转录显著增强。增加幅度从10倍到近40倍不等。众所周知，SPIT基因的表达也响应于几种环境条件而被调节。我们发现，离子的破坏并没有取消高氧或低渗透压条件下的hilA和sipC表达的抑制，这表明Lon通过独立于这些环境信号的调节途径抑制SPIT基因表达。由于HilA被认为是SPIT基因表达的中心调节因子，因此推测Lon可能通过蛋白水解激活HilA表达所需的假定因子来调节SPIT基因表达。
An early step in the pathogenesis of Salmonella enterica serovar Typhimurium infection is bacterial penetration of the intestinal epithelium. Penetration requires the expression of invasion genes found in Salmonella pathogenicity island 1 (SPIT). These genes are controlled in a complex manner by regulators in SPIT, including HilA and InvF, and those outside SPIT, such as two-component regulatory systems and small DNA-binding proteins. We report here that the expression of invasion genes and the invasive phenotype of S. enterica serovar Typhimurium are negatively regulated by the ATP-dependent Lon protease, which is known to be a major contributor to proteolysis in Escherichia coli. A disrupted mutant of ton was able to efficiently invade cultured epithelial cells and showed increased production and secretion of three identified SPIT proteins, SipA, SipC, and SipD. The Ion mutant also showed a dramatic enhancement in transcription of the SPIT genes hilA, invF, sipA, and sipC. The increases ranged from 10-fold to almost 40-fold. It is well known that the expression of SPIT genes is also regulated in response to several environmental conditions. We found that the disruption of Ion does not abolish the repression of hilA and sipC expression by high-oxygen or low-osmolarity conditions, suggesting that Lon represses SPIT gene expression by a regulatory pathway independent of these environmental signals. Since HilA is thought to function as a central regulator of SPIT gene expression, it is speculated that Lon may regulate SPIT gene expression by proteolysis of putative factors required for activation of hilA expression.