Department of Biophysics and Chemical Biology, Seoul National University, Seoul, 08826, Republic of Korea.
School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, 08826, Republic of Korea.
NPJ Biofilms Microbiomes. 2022 Aug 20;8(1):65. doi: 10.1038/s41522-022-00331-x.
In addition to catalyzing coupled transport and phosphorylation of carbohydrates, the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulates various physiological processes in most bacteria. Therefore, the transcription of genes encoding the PTS is precisely regulated by transcriptional regulators depending on substrate availability. As the distribution of the mannose-specific PTS (PTS) is limited to animal-associated bacteria, it has been suggested to play an important role in host-bacteria interactions. In Vibrio cholerae, mannose is known to inhibit biofilm formation. During host infection, the transcription level of the V. cholerae gene encoding the putative PTS (hereafter referred to as manP) significantly increases, and mutations in this gene increase host survival rate. Herein, we show that an AraC-type transcriptional regulator (hereafter referred to as ManR) acts as a transcriptional activator of the mannose operon and is responsible for V. cholerae growth and biofilm inhibition on a mannose or fructose-supplemented medium. ManR activates mannose operon transcription by facilitating RNA polymerase binding to the promoter in response to mannose 6-phosphate and, to a lesser extent, to fructose 1-phosphate. When manP or manR is impaired, the mannose-induced inhibition of biofilm formation was reversed and intestinal colonization was significantly reduced in a Drosophila melanogaster infection model. Our results show that ManR recognizes mannose and fructose in the environment and facilitates V. cholerae survival in the host.
除了催化碳水化合物的偶联运输和磷酸化外，磷酸烯醇丙酮酸：碳水化合物磷酸转移酶系统 (PTS) 还调节大多数细菌的各种生理过程。因此，编码 PTS 的基因的转录受转录调节剂根据底物可用性进行精确调节。由于甘露糖特异性 PTS（PTS）的分布仅限于与动物相关的细菌，因此它被认为在宿主-细菌相互作用中发挥重要作用。在霍乱弧菌中，甘露糖已知会抑制生物膜的形成。在宿主感染期间，霍乱弧菌基因编码假定 PTS（以下简称 manP）的转录水平显著增加，并且该基因的突变会增加宿主的存活率。在此，我们表明 AraC 型转录调节因子（以下简称 ManR）作为甘露糖操纵子的转录激活剂，负责甘露糖或果糖补充培养基上霍乱弧菌的生长和生物膜抑制。ManR 通过促进 RNA 聚合酶与启动子结合来响应甘露糖 6-磷酸并在较小程度上响应果糖 1-磷酸来激活甘露糖操纵子转录。当 manP 或 manR 受损时，甘露糖诱导的生物膜形成抑制作用被逆转，并且在果蝇感染模型中肠道定植显著减少。我们的结果表明，ManR 识别环境中的甘露糖和果糖，并促进霍乱弧菌在宿主中的存活。
