Columbia University, New York, NY 10032, USA.
J Bacteriol. 2011 Mar;193(5):1034-41. doi: 10.1128/JB.00694-10. Epub 2010 Dec 17.
Lactobacillus iners is a common constituent of the human vaginal microbiota. This species was only recently characterized due to its fastidious growth requirements and has been hypothesized to play a role in the pathogenesis of bacterial vaginosis. Here we present the identification and molecular characterization of a protein toxin produced by L. iners. The L. iners genome encodes an open reading frame with significant primary sequence similarity to intermedilysin (ILY; 69.2% similarity) and vaginolysin (VLY; 68.4% similarity), the cholesterol-dependent cytolysins from Streptococcus intermedius and Gardnerella vaginalis, respectively. Clinical isolates of L. iners produce this protein, inerolysin (INY), during growth in vitro, as assessed by Western analysis. INY is a pore-forming toxin that is activated by reducing agents and inhibited by excess cholesterol. It is active across a pH range of 4.5 to 6.0 but is inactive at pH 7.4. At sublytic concentrations, INY activates p38 mitogen-activated protein kinase and allows entry of fluorescent phalloidin into the cytoplasm of epithelial cells. Unlike VLY and ILY, which are human specific, INY is active against cells from a broad range of species. INY represents a new target for studies directed at understanding the role of L. iners in states of health and disease at the vaginal mucosal surface.
阴道内乳杆菌是人类阴道微生物群的常见组成部分。由于其苛刻的生长要求，该物种最近才被描述，并被假设在细菌性阴道病的发病机制中发挥作用。在这里，我们介绍了由阴道内乳杆菌产生的一种蛋白毒素的鉴定和分子特征。阴道内乳杆菌基因组编码一个开放阅读框，与链球菌中介素（ILY；69.2%相似性）和阴道加德纳菌溶素（VLY；68.4%相似性）具有显著的一级序列相似性，分别为链球菌中介和阴道加德纳菌的胆固醇依赖性细胞溶解素。通过 Western 分析评估，临床分离株的阴道内乳杆菌在体外生长过程中产生这种蛋白，内溶素（INY）。INY 是一种形成孔的毒素，被还原剂激活，被过量胆固醇抑制。它在 pH 值为 4.5 到 6.0 的范围内具有活性，但在 pH 值为 7.4 时没有活性。在亚致死浓度下，INY 激活 p38 丝裂原活化蛋白激酶，并允许荧光鬼笔环肽进入上皮细胞的细胞质。与专门针对人类的 VLY 和 ILY 不同，INY 对来自广泛物种的细胞具有活性。INY 代表了针对在阴道黏膜表面健康和疾病状态下理解阴道内乳杆菌作用的研究的新目标。
