Virulent aggregates of Streptococcus pyogenes are generated by homophilic protein-protein interactions
Virulent aggregates of Streptococcus pyogenes are generated by homophilic protein-protein interactions
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DOI：
10.1046/j.1365-2958.2000.02084.x
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发表时间：
2000-09-01
影响因子：
3.6
通讯作者：
Björck, L
中科院分区：
文献类型：
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作者：
Frick, IM;Mörgelin, M;Björck, L
重要的人类病原体化脓性链球菌的许多菌株在体外液体培养基中生长时会形成聚集体。目前的研究表明，这一特性对于化脓性链球菌的粘附、吞噬作用抵抗和毒力至关重要。在常见化脓性链球菌血清型的表面蛋白中鉴定出 19 个氨基酸残基的保守序列（称为 AHP）。人们发现该序列通过邻近细菌的含有 AHP 的表面蛋白之间的同亲蛋白-蛋白相互作用促进细菌聚集。合成的 AHP 肽可抑制化脓性链球菌聚集，降低化脓性链球菌在人血液中的存活率，并减弱其对小鼠的毒力。相反，缺乏含有 AHP 相关序列的表面蛋白的突变细菌不会聚集或粘附到上皮细胞。这些细菌在人类血液中也会被迅速杀死，并且在小鼠中表现出毒力降低，这强调了 AHP 序列和化脓性链球菌聚集的致病意义。
Many strains of the important human pathogen Streptococcus pyogenes form aggregates when grown in vitro in liquid medium. The present studies demonstrate that this property is crucial for the adherence, the resistance to phagocytosis and the virulence of S. pyogenes. A conserved sequence of 19 amino acid residues (designated AHP) was identified in surface proteins of common S. pyogenes serotypes. This sequence was found to promote bacterial aggregation through homophilic protein-protein interactions between AHP-containing surface proteins of neighbouring bacteria. A synthetic AHP peptide inhibited S. pyogenes aggregation, reduced the survival of S. pyogenes in human blood and attenuated its virulence in mice. In contrast, mutant bacteria devoid of surface proteins containing AHP-related sequences did not aggregate or adhere to epithelial cells. These bacteria are also rapidly killed in human blood and show reduced virulence in mice, underlining the pathogenic significance of the AHP sequence and S. pyogenes aggregation.