National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, and Center for Food and Bioconvergence, Seoul National University, Seoul, South Korea.
Infect Immun. 2013 Oct;81(10):3721-30. doi: 10.1128/IAI.00561-13. Epub 2013 Jul 29.
Quorum sensing is a cell-to-cell communication system known to control many bacterial processes. In the present study, the functions of quorum sensing in the pathogenesis of Vibrio vulnificus, a food-borne pathogen, were assessed by evaluating the virulence of a mutant deficient in SmcR, a quorum-sensing regulator and homologue of LuxR. When biofilms were used as an inoculum, the smcR mutant was impaired in virulence and colonization capacity in the infection of mice. The lack of SmcR also resulted in decreased histopathological damage in mouse jejunum tissue. These results indicated that SmcR is essential for V. vulnificus pathogenesis. Moreover, the smcR mutant exhibited significantly reduced biofilm detachment. Upon exposure to INT-407 host cells, the wild type, but not the smcR mutant, revealed accelerated biofilm detachment. The INT-407 cells increased smcR expression by activating the expression of LuxS, an autoinducer-2 synthase, indicating that host cells manipulate the cellular level of SmcR through the quorum-sensing signaling of V. vulnificus. A whole-genome microarray analysis revealed that the genes primarily involved in biofilm detachment and formation are up- and downregulated by SmcR, respectively. Among the SmcR-regulated genes, vvpE encoding an elastolytic protease was the most upregulated, and the purified VvpE appeared to dissolve established biofilms directly in a concentration-dependent manner in vitro. These results suggest that the host cell-induced SmcR enhances the detachment of V. vulnificus biofilms entering the host intestine and thereby may promote the dispersal of the pathogen to new colonization loci, which is crucial for pathogenesis.
群体感应是一种细胞间通讯系统，已知它可以控制许多细菌过程。在本研究中，通过评估 SmcR 缺陷突变体的毒力来评估群体感应在食源性病原体创伤弧菌发病机制中的作用，SmcR 是一种群体感应调节剂和 LuxR 的同源物。当生物膜被用作接种物时，smcR 突变体在感染小鼠时的毒力和定植能力受损。SmcR 的缺乏也导致小鼠空肠组织的组织病理学损伤减少。这些结果表明 SmcR 是创伤弧菌发病机制所必需的。此外，smcR 突变体表现出明显减少的生物膜脱落。当暴露于 INT-407 宿主细胞时，野生型，但不是 smcR 突变体，显示出加速的生物膜脱落。INT-407 细胞通过激活自动诱导物-2 合酶 LuxS 的表达来增加 smcR 的表达，表明宿主细胞通过创伤弧菌的群体感应信号来操纵 SmcR 的细胞水平。全基因组微阵列分析表明，主要参与生物膜脱落和形成的基因分别被 SmcR 上调和下调。在 SmcR 调节的基因中，编码弹性蛋白酶的 vvpE 基因表达上调最明显，纯化的 VvpE 似乎可以直接在体外以浓度依赖的方式溶解已建立的生物膜。这些结果表明，宿主细胞诱导的 SmcR 增强了进入宿主肠道的创伤弧菌生物膜的脱落，从而可能促进病原体向新的定植部位扩散，这对发病机制至关重要。
