Ness Stefan, Hilleringmann Markus
FG Protein Biochemistry & Cellular Microbiology, Department of Applied Sciences and Mechatronics, Munich University of Applied Sciences, Munich, Germany.
Front Microbiol. 2021 Feb 9;12:615924. doi: 10.3389/fmicb.2021.615924. eCollection 2021.
represents a major Gram-positive human pathogen causing bacterial pneumonia, otitis media, meningitis, and other invasive diseases. Several pneumococcal isolates show increasing resistance rates against antibacterial agents. A variety of virulence factors promote pneumococcal pathogenicity with varying importance in different stages of host infection. Virulence related hair-like structures ("pili") are complex, surface located protein arrays supporting proper host interaction. In the last two decades different types of pneumococcal pili have been identified: pilus-1 (P1) and pilus-2 (P2) are formed by the catalytic activity of sortases that covalently assemble secreted polypeptide pilin subunits in a defined order and finally anchor the resulting pilus in the peptidoglycan. Within the long pilus fiber the presence of intramolecular isopeptide bonds confer high stability to the sequentially arranged individual pilins. This mini review will focus on TIGR4 P1 molecular architecture, the subunits it builds and provides insights into P1 sortase-mediated assembly. The complex P1 architecture (anchor-/backbone-/tip-subunits) allows the specific interaction with various target structures facilitating different steps of colonization, invasion and spreading within the host. Optimized pilin subunit confirmation supports P1 function under physiological conditions. Finally, aspects of P1- host interplay are summarized, including recent insights into P1 mechanobiology, which have important implications for P1 mediated pathogenesis.
是一种主要的革兰氏阳性人类病原体，可引起细菌性肺炎、中耳炎、脑膜炎和其他侵袭性疾病。几种肺炎球菌分离株对抗菌剂的耐药率不断上升。多种毒力因子促进肺炎球菌的致病性，在宿主感染的不同阶段具有不同程度的重要性。与毒力相关的毛发状结构（“菌毛”）是复杂的表面定位蛋白阵列，有助于与宿主进行适当的相互作用。在过去二十年中，已鉴定出不同类型的肺炎球菌菌毛：菌毛-1（P1）和菌毛-2（P2）是由分选酶的催化活性形成的，分选酶以确定的顺序共价组装分泌的多肽菌毛蛋白亚基，并最终将产生的菌毛锚定在肽聚糖中。在长菌毛纤维内，分子内异肽键的存在赋予了依次排列的单个菌毛蛋白高度的稳定性。本综述将重点关注TIGR4 P1的分子结构、其构建的亚基，并深入探讨P1分选酶介导的组装过程。复杂的P1结构（锚定/主干/尖端亚基）允许与各种靶结构进行特异性相互作用，从而促进在宿主体内定殖、侵袭和扩散的不同步骤。优化的菌毛蛋白亚基构象在生理条件下支持P1的功能。最后，总结了P1与宿主相互作用的各个方面，包括对P1力学生物学的最新见解，这些见解对P1介导的发病机制具有重要意义。
