Agaisse H, Gominet M, Okstad O A, Kolstø A B, Lereclus D
Unité de Biochimie Microbienne, Centre National de la Recherche Scientifique URA 1300, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Mol Microbiol. 1999 Jun;32(5):1043-53. doi: 10.1046/j.1365-2958.1999.01419.x.
Members of the Bacillus cereus group (B. anthracis, B. cereus, B. mycoides and B. thuringiensis) are well-known pathogens of mammals (B. anthracis and B. cereus) and insects (B. thuringiensis). The specific diseases they cause depend on their capacity to produce specific virulence factors, such as the lethal toxin of B. anthracis and the Cry toxins of B. thuringiensis. However, these Bacillus spp. also produce a variety of proteins, such as phospholipases C, which are known to act as virulence factors in various pathogenic bacteria. Few genes encoding these virulence factors have been characterized in pathogenic Bacillus spp. and little is known about the regulation of their expression. We had previously reported that in B. thuringiensis expression of the phosphatidylinositol-specific phospholipase C gene is regulated by the transcriptional activator PlcR. Here we report the identification of several extracellular virulence factor genes by the virtue of their PlcR-regulated expression. These PlcR-regulated genes encode degradative enzymes, cell-surface proteins and enterotoxins. The PlcR-regulated genes are widely dispersed on the chromosome and therefore do not constitute a pathogenic island. Analysis of the promoter region of the PlcR-regulated genes revealed the presence of a highly conserved palindromic region (TATGNAN4TNCATA), which is presumably the specific recognition target for PlcR activation. We found that the plcR gene is also present in and probably restricted to all the members of the B. cereus group. However, although the polypeptide encoded by the B. cereus PlcR gene is functionally equivalent to the B. thuringiensis regulator, the polypeptide encoded by the B. anthracis gene is truncated and not active as a transcriptional activator. PlcR is the first example described of a pleiotropic regulator involved in the control of extracellular virulence factor expression in pathogenic Bacillus spp. These results have implications for the taxonomic relationships among members of the B. cereus group, the virulence properties of these bacteria and the safety of B. thuringiensis-based biopesticides.
蜡样芽孢杆菌群（炭疽芽孢杆菌、蜡样芽孢杆菌、蕈状芽孢杆菌和苏云金芽孢杆菌）的成员是哺乳动物（炭疽芽孢杆菌和蜡样芽孢杆菌）和昆虫（苏云金芽孢杆菌）的著名病原体。它们引发的特定疾病取决于其产生特定毒力因子的能力，例如炭疽芽孢杆菌的致死毒素和苏云金芽孢杆菌的Cry毒素。然而，这些芽孢杆菌属还产生多种蛋白质，如磷脂酶C，已知其在各种病原菌中作为毒力因子起作用。在致病性芽孢杆菌属中，很少有编码这些毒力因子的基因得到表征，对其表达调控也知之甚少。我们之前曾报道，在苏云金芽孢杆菌中，磷脂酰肌醇特异性磷脂酶C基因的表达受转录激活因子PlcR调控。在此我们报告，通过其受PlcR调控的表达鉴定出了几个细胞外毒力因子基因。这些受PlcR调控的基因编码降解酶、细胞表面蛋白和肠毒素。受PlcR调控的基因广泛分散在染色体上，因此不构成致病岛。对受PlcR调控基因的启动子区域分析揭示存在一个高度保守的回文区域（TATGNAN4TNCATA），推测这是PlcR激活的特异性识别靶点。我们发现plcR基因也存在于蜡样芽孢杆菌群的所有成员中，并且可能仅限于此。然而，尽管蜡样芽孢杆菌PlcR基因编码的多肽在功能上等同于苏云金芽孢杆菌的调节因子，但炭疽芽孢杆菌基因编码的多肽被截短，作为转录激活因子无活性。PlcR是描述的第一个参与控制致病性芽孢杆菌属细胞外毒力因子表达的多效调节因子的例子。这些结果对蜡样芽孢杆菌群成员之间的分类关系、这些细菌的毒力特性以及基于苏云金芽孢杆菌的生物杀虫剂的安全性具有重要意义。
