Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation

Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation
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DOI:
10.1111/j.1365-2958.2007.05704.x
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发表时间:
2007-05-01
影响因子:
3.6
通讯作者:
Margarit, Immaculada
Margarit, Immaculada
中科院分区:
生物学2区
文献类型:
--
作者:
Manetti, Andrea G. O.;Zingaretti, Chiara;Margarit, Immaculada

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A群链球菌(GAS,化脓性链球菌)是一种革兰氏阳性人类病原体,可导致几种急性疾病和自身免疫性后遗症,每年在全球造成50万人死亡。GAS感染需要病原体附着在宿主组织上并聚集成细胞聚集体的能力。此外,最近还提出了生物膜在GAS发病机制中的作用。本文研究了GAS菌毛在生物膜形成中的作用。我们证明了GAS菌毛阴性突变体,其中编码菌毛主干结构蛋白或分选酶C1的基因被删除,显示出附着在咽细胞系上的能力受损。同样的突变体在液体培养中形成细胞聚集体和在人细胞上形成微菌落的效率要低得多。此外,突变菌株不能产生典型的三维层,细菌微菌落嵌入碳水化合物聚合物基质。互补突变体具有与野生型菌株相似的粘附和聚集表型。最后,间接证实了毛的体内表达,证实了大多数gas介导咽炎患者的血清都能识别重组毛蛋白。这些数据支持毛在GAS粘附和定植中的作用,并提示毛在所有致病性链球菌中的一般作用。
Group A Streptococcus ( GAS, Streptococcus pyogenes) is a Gram-positive human pathogen responsible for several acute diseases and autoimmune sequelae that account for half a million deaths worldwide every year. GAS infections require the capacity of the pathogen to adhere to host tissues and assemble in cell aggregates. Furthermore, a role for biofilms in GAS pathogenesis has recently been proposed. Here we investigated the role of GAS pili in biofilm formation. We demonstrated that GAS pilus-negative mutants, in which the genes encoding either the pilus backbone structural protein or the sortase C1 have been deleted, showed an impaired capacity to attach to a pharyngeal cell line. The same mutants were much less efficient in forming cellular aggregates in liquid culture and microcolonies on human cells. Furthermore, mutant strains were incapable of producing the typical three-dimensional layer with bacterial microcolonies embedded in a carbohydrate polymeric matrix. Complemented mutants had an adhesion and aggregation phenotype similar to the wild-type strain. Finally, in vivo expression of pili was indirectly confirmed by demonstrating that most of the sera from human patients affected by GAS-mediated pharyngitis recognized recombinant pili proteins. These data support the role of pili in GAS adherence and colonization and suggest a general role of pili in all pathogenic streptococci.