Bistable Expression of CsgD in Salmonella enterica Serovar Typhimurium Connects Virulence to Persistence
Bistable Expression of CsgD in Salmonella enterica Serovar Typhimurium Connects Virulence to Persistence
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DOI：
10.1128/iai.00137-15
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发表时间：
2015-06-01
影响因子：
3.1
通讯作者：
White, Aaron P.
中科院分区：
文献类型：
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作者：
MacKenzie, Keith D.;Wang, Yejun;White, Aaron P.
致病细菌通常需要在宿主和环境中生存，目前还不清楚细胞如何在这些同样具有挑战性的情况之间过渡。对于人类和动物病原体沙门氏菌鼠伤寒血清型，生物膜形成与宿主外的持久性相关，但与毒力的联系尚不清楚。在这项研究中，我们分析了S.鼠伤寒杆菌在生物膜诱导条件下生长。这些细胞类型的出现是由于CsgD的过度表达，CsgD是中心生物膜调节因子。尽管暴露于相同的压力下，这两个细胞亚群有1，856个差异表达的基因，如通过转录组测序（RNA-seq）所确定的。聚集的细胞显示生物膜的特征性基因表达，而增殖细胞具有增强的许多毒力基因的表达。与聚集体相比，在人肠细胞系中增加的第三型分泌合成与增强的侵袭相关，并且在小鼠中显著增加毒力。然而，当同一组细胞暴露于干燥时，聚集体存活得更好，并且缺乏细胞的竞争优势。我们假设，CsgD为基础的分化是一种形式的赌注对冲，与单细胞启动宿主细胞入侵和聚集的细胞适应持久性的环境。这使得S。鼠伤寒沙门氏菌传播的风险，并确保宿主和环境之间的平稳过渡。
Pathogenic bacteria often need to survive in the host and the environment, and it is not well understood how cells transition between these equally challenging situations. For the human and animal pathogen Salmonella enterica serovar Typhimurium, biofilm formation is correlated with persistence outside a host, but the connection to virulence is unknown. In this study, we analyzed multicellular-aggregate and planktonic-cell subpopulations that coexist when S. Typhimurium is grown under biofilminducing conditions. These cell types arise due to bistable expression of CsgD, the central biofilm regulator. Despite being exposed to the same stresses, the two cell subpopulations had 1,856 genes that were differentially expressed, as determined by transcriptome sequencing (RNA-seq). Aggregated cells displayed the characteristic gene expression of biofilms, whereas planktonic cells had enhanced expression of numerous virulence genes. Increased type three secretion synthesis in planktonic cells correlated with enhanced invasion of a human intestinal cell line and significantly increased virulence in mice compared to the aggregates. However, when the same groups of cells were exposed to desiccation, the aggregates survived better, and the competitive advantage of planktonic cells was lost. We hypothesize that CsgD-based differentiation is a form of bet hedging, with single cells primed for host cell invasion and aggregated cells adapted for persistence in the environment. This allows S. Typhimurium to spread the risks of transmission and ensures a smooth transition between the host and the environment.