Fulde M, Bernardo-García N, Rohde M, Nachtigall N, Frank R, Preissner K T, Klett J, Morreale A, Chhatwal G S, Hermoso J A, Bergmann S
Simone Bergmann, PhD, Technische Universität Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany, Tel.: +49 531 391 5818, Fax: +49 531 391 5854, E-mail:
Thromb Haemost. 2014 Mar 3;111(3):401-16. doi: 10.1160/TH13-05-0421. Epub 2013 Nov 7.
Streptococcus pneumoniae is not only a commensal of the nasopharyngeal epithelium, but may also cause life-threatening diseases. Immune-electron microscopy studies revealed that the bacterial glycolytic enzyme, phosphoglycerate kinase (PGK), is localised on the pneumococcal surface of both capsulated and non-capsulated strains and colocalises with plasminogen. Since pneumococci may concentrate host plasminogen (PLG) together with its activators on the bacterial cell surface to facilitate the formation of plasmin, the involvement of PGK in this process was studied. Specific binding of human or murine PLG to strain-independent PGK was documented, and surface plasmon resonance analyses indicated a high affinity interaction with the kringle domains 1-4 of PLG. Crystal structure determination of pneumococcal PGK together with peptide array analysis revealed localisation of PLG-binding site in the N-terminal region and provided structural motifs for the interaction with PLG. Based on structural analysis data, a potential interaction of PGK with tissue plasminogen activator (tPA) was proposed and experimentally confirmed by binding studies, plasmin activity assays and thrombus degradation analyses.
肺炎链球菌不仅是鼻咽上皮的共生菌，还可能引发危及生命的疾病。免疫电子显微镜研究表明，细菌糖酵解酶磷酸甘油酸激酶（PGK）定位于有荚膜和无荚膜菌株的肺炎球菌表面，且与纤溶酶原共定位。由于肺炎球菌可能将宿主纤溶酶原（PLG）及其激活剂聚集在细菌细胞表面以促进纤溶酶的形成，因此对PGK在这一过程中的作用进行了研究。已证明人或鼠PLG与不依赖菌株的PGK存在特异性结合，表面等离子体共振分析表明其与PLG的kringle结构域1 - 4存在高亲和力相互作用。肺炎球菌PGK的晶体结构测定以及肽阵列分析揭示了PLG结合位点位于N端区域，并提供了与PLG相互作用的结构基序。基于结构分析数据，提出了PGK与组织纤溶酶原激活剂（tPA）的潜在相互作用，并通过结合研究、纤溶酶活性测定和血栓降解分析进行了实验证实。
