Jönsson Klas, Guo Betty P, Monstein Hans-Jürg, Mekalanos John J, Kronvall Göran
Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1852-7. doi: 10.1073/pnas.0307329101. Epub 2004 Feb 9.
Helicobacter pylori binds a number of host cell proteins, including the plasma protein plasminogen, which is the proenzyme of the serine protease plasmin. Two H. pylori plasminogen-binding proteins have been described; however, no genes were identified. Here we report the use of a phage display library to clone two genes from the H. pylori CCUG 17874 genome that mediate binding to plasminogen. DNA sequence analysis of one of these genes revealed 96.6% homology with H. pylori 26695 HP0508. A subsequent database search revealed that the amino acid sequence of a lysine-rich C-terminal segment of HP0508 is identical to the C terminus of HP0863. Recombinant proteins expressed from HP0508 and HP0863 bound plasminogen specifically and in a lysine-dependent manner. We designate these genes pgbA and pgbB, respectively. These proteins are expressed by a variety of H. pylori strains, have surface-exposed domains, and do not inhibit plasminogen activation. These results indicate that pgbA and pgbB may allow H. pylori to coat its exterior with plasminogen, which subsequently can be activated to plasmin. The surface acquisition of protease activity may enhance the virulence of H. pylori.
幽门螺杆菌可结合多种宿主细胞蛋白，包括血浆蛋白纤溶酶原，它是丝氨酸蛋白酶纤溶酶的酶原。已描述了两种幽门螺杆菌纤溶酶原结合蛋白；然而，尚未鉴定出相关基因。在此，我们报告利用噬菌体展示文库从幽门螺杆菌CCUG 17874基因组中克隆出两个介导与纤溶酶原结合的基因。对其中一个基因的DNA序列分析显示，其与幽门螺杆菌26695的HP0508有96.6%的同源性。随后的数据库搜索表明，HP0508富含赖氨酸的C末端片段的氨基酸序列与HP0863的C末端相同。从HP0508和HP0863表达的重组蛋白特异性地且以赖氨酸依赖的方式结合纤溶酶原。我们分别将这些基因命名为pgbA和pgbB。这些蛋白由多种幽门螺杆菌菌株表达，具有表面暴露结构域，且不抑制纤溶酶原激活。这些结果表明，pgbA和pgbB可能使幽门螺杆菌表面覆盖纤溶酶原，随后纤溶酶原可被激活为纤溶酶。蛋白酶活性在表面的获得可能增强幽门螺杆菌的毒力。
