Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, Minami-josanjima-cho, Tokushima 770-8506, Japan.
Infect Immun. 2010 Sep;78(9):4012-21. doi: 10.1128/IAI.00113-10. Epub 2010 Jul 12.
Streptococcus intermedius is an opportunistic pathogen of humans that causes purulent infections, including brain and liver abscesses. This pathogen secretes a human-specific cytolysin, intermedilysin, which has been recognized as a major virulence factor. However, most of the expressional control mechanisms of ily are still unknown. To determine these mechanisms, we analyzed the nucleotide sequence of the ily promoter region. We found a highly homologous region to the catabolite-repressible element (cre) in the ily promoter region and observed a considerable decrease in the amount of secreted intermedilysin when cells were grown in a culture medium containing high concentrations of glucose/utilizable carbohydrates. Disruption of the ccpA gene, which encodes catabolite control protein A, did not induce catabolite repression of ily by glucose/utilizable carbohydrates. In cre mutants, catabolite repression of ily was partially restored, and purified catabolite control protein A bound to an oligonucleotide containing the cre consensus sequence in the ily promoter region. In addition, a prolonged lag phase and slower doubling time of the ccpA mutant cells were observed. Our data show that S. intermedius can modulate ily expression and growth rate through catabolite control protein A-mediated monitoring of the extracellular glucose/utilizable carbohydrate concentration.
中间链球菌是一种人类机会致病菌，可引起化脓性感染，包括脑脓肿和肝脓肿。该病原体分泌一种人类特异性细胞毒素，即中间溶素，已被认为是主要的毒力因子。然而，ily 的大多数表达调控机制仍不清楚。为了确定这些机制，我们分析了 ily 启动子区域的核苷酸序列。我们在 ily 启动子区域发现了一个与分解代谢物阻遏元件 (cre) 高度同源的区域，并且当细胞在含有高浓度葡萄糖/可利用碳水化合物的培养基中生长时，分泌的中间溶素数量明显减少。ccpA 基因（编码分解代谢物控制蛋白 A）的破坏并没有诱导葡萄糖/可利用碳水化合物对 ily 的分解代谢物抑制。在 cre 突变体中，ily 的分解代谢物抑制部分得到恢复，并且纯化的分解代谢物控制蛋白 A 与含有 cre 共有序列的寡核苷酸结合在 ily 启动子区域。此外，观察到 ccpA 突变体细胞的迟滞期延长和倍增时间变慢。我们的数据表明，中间链球菌可以通过细胞外葡萄糖/可利用碳水化合物浓度的分解代谢物控制蛋白 A 介导的监测来调节 ily 的表达和生长速率。
