Department of Frontier Bioscience, Faculty of Bioscience and Applied Chemistry, Hosei University, Tokyo, Japan.
Infect Immun. 2012 Sep;80(9):3170-8. doi: 10.1128/IAI.00039-12. Epub 2012 Jul 2.
The chemotaxis of Vibrio cholerae, the causative agent of cholera, has been implicated in pathogenicity. The bacterium has more than 40 genes for methyl-accepting chemotaxis protein (MCP)-like proteins (MLPs). In this study, we found that glycine and at least 18 L-amino acids, including serine, arginine, asparagine, and proline, serve as attractants to the classical biotype strain O395N1. Based on the sequence comparison with Vibrio parahaemolyticus, we speculated that at least 17 MLPs of V. cholerae may mediate chemotactic responses. Among them, Mlp24 (previously named McpX) is required for the production of cholera toxin upon mouse infection. mlp24 deletion strains of both classical and El Tor biotypes showed defects in taxis toward several amino acids, which were complemented by the expression of Mlp24. These amino acids enhanced methylation of Mlp24. Serine, arginine, asparagine, and proline were shown to bind directly to the periplasmic fragment of Mlp24. The structural information of its closest homolog, Mlp37, predicts that Mlp24 has two potential ligand-binding pockets per subunit, the membrane distal of which was suggested, by mutational analyses, to be involved in sensing of amino acids. These results suggest that Mlp24 is a chemoreceptor for multiple amino acids, including serine, arginine, and asparagine, which were previously shown to stimulate the expression of several virulence factors, implying that taxis toward a set of amino acids plays critical roles in pathogenicity of V. cholerae.
霍乱弧菌的趋化性与致病性有关,这种细菌有超过 40 个用于甲基受体趋化蛋白(MCP)样蛋白(MLP)的基因。在这项研究中,我们发现甘氨酸和至少 18 种 L-氨基酸,包括丝氨酸、精氨酸、天冬酰胺和脯氨酸,可作为经典生物型菌株 O395N1 的吸引剂。基于与副溶血性弧菌的序列比较,我们推测霍乱弧菌至少有 17 个 MLPs 可能介导趋化反应。其中,Mlp24(以前称为 McpX)是在感染小鼠时产生霍乱毒素所必需的。经典和 El Tor 生物型的 mlp24 缺失菌株在向几种氨基酸的趋化性方面存在缺陷,这些缺陷可以通过表达 Mlp24 来弥补。这些氨基酸增强了 Mlp24 的甲基化。丝氨酸、精氨酸、天冬酰胺和脯氨酸被证明可以直接与 Mlp24 的周质片段结合。其最接近的同源物 Mlp37 的结构信息表明,每个亚基都有两个潜在的配体结合口袋,膜远端的口袋通过突变分析表明参与了氨基酸的感应。这些结果表明,Mlp24 是多种氨基酸的化学感受器,包括丝氨酸、精氨酸和天冬酰胺,这些氨基酸以前被证明可以刺激几种毒力因子的表达,这表明向一组氨基酸的趋化性在霍乱弧菌的致病性中起着关键作用。