The RcsB-RcsC regulatory system of Salmonella typhi differentially modulates the expression of invasion proteins, flagellin and Vi antigen in response to osmolarity
The RcsB-RcsC regulatory system of Salmonella typhi differentially modulates the expression of invasion proteins, flagellin and Vi antigen in response to osmolarity
复制标题
DOI：
10.1046/j.1365-2958.1998.00976.x
复制
发表时间：
1998-08-01
影响因子：
3.6
通讯作者：
Popoff, MY
中科院分区：
文献类型：
--
作者：
Arricau, N;Hermant, D;Popoff, MY
进入肠上皮细胞是伤寒沙门氏菌致病性的一个重要特征，伤寒沙门氏菌可导致人类伤寒。这一过程需要完整的运动能力以及促进侵袭的Sip蛋白的分泌，这些蛋白是由inv、spa和prg位点编码的III型分泌系统的作用靶点。在我们对伤寒沙门氏菌进入培养的上皮细胞的研究过程中，我们观察到在表达Vi的菌株中，Sip蛋白和鞭毛蛋白的分泌受到损害。我们在此报道，Sip蛋白、鞭毛蛋白和Vi抗原的产生受到RcsB - RcsC调控系统和渗透压的差异调节。这种调节发生在转录水平和翻译后水平。在低渗透压条件下，iagA、invF和sipB基因的转录受到RcsB调节因子的负调控，该调节因子可能与viaB位点编码的TviA蛋白协同作用。在这些生长条件下大量产生的细胞表面相关的Vi多糖阻止了Sip蛋白和鞭毛蛋白的分泌。随着生长培养基中NaCl浓度的增加，发现iagA、invF和sipB的转录显著增加，而参与Vi抗原生物合成的基因的转录则大幅减少。iagA的表达（其产物参与InvF和sipB的转录）在指数生长期选择性地发生，并且在300 mM NaCl存在时达到最大值。在这种渗透压下，大量的Sip蛋白和鞭毛蛋白分泌到培养上清液中。正如从这些结果所预期的那样，并且鉴于Sip蛋白和运动能力在进入细胞过程中的关键作用，RcsB和渗透压调节了伤寒沙门氏菌的侵袭能力。总之，这些发现可能反映了伤寒沙门氏菌对发病机制不同阶段所遇到环境的适应性反应。
Entry into intestinal epithelial cells is an essential feature in the pathogenicity of Salmonella typhi, which causes typhoid fever in humans. This process requires intact motility and secretion of the invasion-promoting Sip proteins, which are targets of the type III secretion machinery encoded by the inv, spa and prg loci. During our investigations into the entry of S. typhi into cultured epithelial cells, we observed that the secretion of Sip proteins and flagellin was impaired in Vi-expressing strains. We report here that the production of Sip proteins, flagellin and Vi antigen is differentially modulated by the RcsB-RcsC regulatory system and osmolarity. This regulation occurs at both transcriptional and post-translational levels. Under low-osmolarity conditions, the transcription of iagA, invF and sipB genes is negatively controlled by the RcsB regulator, which probably acts in association with the viaB locus-encoded TviA protein, The cell surface-associated Vi polysaccharide, which was maximally produced under these growth conditions, prevented the secretion of Sip proteins and flagellin, As the NaCl concentration in the growth medium was increased, transcription of iagA, invF and sips was found to be markedly increased, whereas transcription of genes involved in Vi antigen biosynthesis was greatly reduced, The expression of iagA, whose product is involved in InvF and sipB transcription, occurred selectively during the exponential growth phase and was maximal in the presence of 300 mM NaCl. At this osmolarity, large amounts ofSips and flagellin were secreted in culture supernatants, As expected from these results, and given the essential role of Sip proteins and motility in entry, RcsB and osmolarity modulated the invasive capacity of S. typhi, Together, these findings might reflect the adaptive response of S. typhi to the environments encountered during the different stages of pathogenesis.