Department of Biological Science and Technology, Institute of Technology and Science, University of Tokushima Graduate School, 2-1 Minamijosanjima-cho, Tokushima, Tokushima, 770-8506.
Microbiol Immunol. 2014 Mar;58(3):155-71. doi: 10.1111/1348-0421.12131.
Cholesterol-dependent cytolysins (CDCs) are bacterial pore-forming toxins secreted mainly by pathogenic Gram-positive bacteria. CDCs generally recognize and bind to membrane cholesterol to create pores and lyse target cells. However, in contrast to typical CDCs such as streptolysin O, several atypical CDCs have been reported. The first of these was intermedilysin, which is secreted by Streptococcus intermedius and has human cell-specificity, human CD59 (huCD59) being its receptor. In the study reported here, the diversity of receptor recognition among CDCs was investigated and multi-receptor recognition characteristics were identified within this toxin family. Streptococcus mitis-derived human platelet aggregation factor (Sm-hPAF) secreted by S. mitis strain Nm-65 isolated from a patient with Kawasaki disease was previously shown to hemolyze erythrocytes in a species-dependent manner, its maximum activity being in human cells. In the present study, it was found that Sm-hPAF recognizes both membrane cholesterol and huCD59 as receptors for triggering pore-formation. Moreover, vaginolysin (VLY) of Gardnerella vaginalis showed similar characteristics to Sm-hPAF regarding receptor recognition. On the basis of the results presented here, the mode of receptor recognition of CDCs can be categorized into the following three groups: (i) Group I, comprising typical CDCs with high affinity to cholesterol and no or very little affinity to huCD59; (ii) Group II, including atypical CDCs such as ILY, with no or very little affinity to cholesterol and high affinity to huCD59; and (iii) Group III, which contains atypical CDCs such as Sm-hPAF and VLY with affinity to both cholesterol and huCD59.
胆固醇依赖性细胞溶素（CDCs）是主要由致病性革兰氏阳性细菌分泌的细菌形成孔的毒素。CDCs 通常识别并结合膜胆固醇以形成孔并裂解靶细胞。然而，与典型的 CDC 如链球菌溶血素 O 不同，已经报道了几种非典型的 CDC。第一个是中介溶素，它由中间链球菌分泌，具有人类细胞特异性，其受体是人 CD59（huCD59）。在本报告中，研究了 CDC 之间受体识别的多样性，并确定了该毒素家族内的多受体识别特征。先前已经表明，从川崎病患者中分离出的链球菌 Nm-65 分泌的人类血小板聚集因子（Sm-hPAF）以物种依赖的方式溶血红细胞，其最大活性在人类细胞中。在本研究中，发现 Sm-hPAF 既识别膜胆固醇又识别 huCD59 作为触发孔形成的受体。此外，加德纳菌阴道溶素（VLY）在受体识别方面表现出与 Sm-hPAF 相似的特征。基于这里提出的结果，可以将 CDC 的受体识别模式分为以下三组：（i）组 I，包含对胆固醇具有高亲和力且对 huCD59 没有或几乎没有亲和力的典型 CDC；（ii）组 II，包括对胆固醇没有或几乎没有亲和力但对 huCD59 具有高亲和力的非典型 CDC，如 ILY；和（iii）组 III，包含对胆固醇和 huCD59 具有亲和力的非典型 CDC，如 Sm-hPAF 和 VLY。
