Department of Biological Science and Technology, Life System, Institute of Technology and Science, Tokushima University Graduate School, Tokushima, Tokushima, Japan.
Department of Bioengineering, Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Graduate School, Tokushima, Tokushima, Japan.
Microbiol Immunol. 2021 Feb;65(2):61-75. doi: 10.1111/1348-0421.12868. Epub 2021 Jan 18.
Streptococcus pseudopneumoniae (SPpn) is a relatively new species closely related to S. pneumoniae (SPn) and S. mitis (SM) belonging to the Mitis group of the genus Streptococcus (MGS). Although genes encoding various pneumococcal virulence factors have been observed in the SPpn genome, the pathogenicity of SPpn against human, including the roles of virulence factor candidates, is still unclear. The present study focused on and characterized a candidate virulence factor previously reported in SPpn with deduced multiple functional domains, such as lipase domain, two lectin domains, and cholesterol-dependent cytolysin-related domain using various recombinant proteins. The gene was found not only in SPpn but also in the strains of SM and SPn. Moreover, the gene product was expressed in the gene-positive strains as secreted and cell-bound forms. The recombinant of gene product showed lipase activity and human cell-binding activity depending on the function of lectin domain(s), but no hemolytic activity. Thus, based on the distribution of the gene within the MGS and its molecular function, the gene product was named mitilectin (MLC) and its contribution to the potential pathogenicity of the MLC-producing strains was investigated. Consequently, the treatment with anti-MLC antibody and the mlc gene-knockout significantly reduced the human cell-binding activity of MLC-producing strains. Therefore, the multifunctional MLC was suggested to be important as an adhesion molecule in considering the potential pathogenicity of the MLC-producing strains belonging to MGS, such as SPpn and SM.
肺炎链球菌（SPn）是一种与肺炎链球菌（SPn）和缓症链球菌（SM）密切相关的相对较新的物种，属于链球菌属的米利坦斯组（MGS）。虽然在 SPpn 基因组中观察到了编码各种肺炎球菌毒力因子的基因，但 SPpn 对人类的致病性，包括候选毒力因子的作用，仍然不清楚。本研究集中研究并表征了先前在 SPpn 中报道的具有推定多种功能结构域（如脂肪酶结构域、两个凝集素结构域和胆固醇依赖性细胞溶解素相关结构域）的候选毒力因子，使用各种重组蛋白。该基因不仅存在于 SPpn 中，也存在于 SM 和 SPn 菌株中。此外，基因产物在基因阳性菌株中以分泌和细胞结合形式表达。重组基因产物表现出脂肪酶活性和与人细胞结合活性，这取决于凝集素结构域的功能，但没有溶血活性。因此，基于该基因在 MGS 中的分布及其分子功能，将该基因产物命名为mitilectin（MLC），并研究了其产生菌的潜在致病性。结果表明，用抗-MLC 抗体和 mlc 基因敲除处理显著降低了 MLC 产生菌的与人细胞结合活性。因此，多功能 MLC 可能作为一种粘附分子，在考虑属于 MGS 的 MLC 产生菌（如 SPpn 和 SM）的潜在致病性方面具有重要意义。
