Streptococcus pneumoniae GAPDH Is Released by Cell Lysis and Interacts with Peptidoglycan.

Streptococcus pneumoniae GAPDH Is Released by Cell Lysis and Interacts with Peptidoglycan.
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DOI:
10.1371/journal.pone.0125377
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Di Guilmi AM
Di Guilmi AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Terrasse R;Amoroso A;Vernet T;Di Guilmi AM

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保守的细胞质蛋白的释放在革兰氏阳性和革兰氏阴性细菌中广泛存在。由于这些蛋白在细菌表面显示出额外的功能,它们被称为兼职蛋白。GAPDH是一种糖酵解酶,在细菌入侵和宿主免疫系统调节等病原微生物的毒力过程中起重要作用。然而,GAPDH与其他兼职蛋白一样,由于不含n端预测信号肽,因此不能通过主动分泌系统分泌。在这项工作中,我们研究了GAPDH在人类主要病原体肺炎链球菌中输出和表面滞留的机制。我们讨论了主要的自溶素LytA在GAPDH传递到细胞表面过程中的作用。在ΔlytA突变株中或在培养基中添加1%氯化胆碱时,肺炎球菌溶解被消除。我们发现,这些条件诱导表面相关的GAPDH数量显著减少。这些数据表明,GAPDH在肺炎球菌细胞表面的存在取决于lyta介导的一小部分细胞群的裂解。此外,我们证明了肺炎球菌GAPDH与细菌细胞壁的结合独立于苔壁酸成分的存在,支持肽聚糖作为表面GAPDH的配体。最后,我们发现肽聚糖相关的GAPDH从人血清中招募C1q,但不激活补体途径。
Release of conserved cytoplasmic proteins is widely spread among Gram-positive and Gram-negative bacteria. Because these proteins display additional functions when located at the bacterial surface, they have been qualified as moonlighting proteins. The GAPDH is a glycolytic enzyme which plays an important role in the virulence processes of pathogenic microorganisms like bacterial invasion and host immune system modulation. However, GAPDH, like other moonlighting proteins, cannot be secreted through active secretion systems since they do not contain an N-terminal predicted signal peptide. In this work, we investigated the mechanism of GAPDH export and surface retention in Streptococcus pneumoniae, a major human pathogen. We addressed the role of the major autolysin LytA in the delivery process of GAPDH to the cell surface. Pneumococcal lysis is abolished in the ΔlytA mutant strain or when 1% choline chloride is added in the culture media. We showed that these conditions induce a marked reduction in the amount of surface-associated GAPDH. These data suggest that the presence of GAPDH at the surface of pneumococcal cells depends on the LytA-mediated lysis of a fraction of the cell population. Moreover, we demonstrated that pneumococcal GAPDH binds to the bacterial cell wall independently of the presence of the teichoic acids component, supporting peptidoglycan as a ligand to surface GAPDH. Finally, we showed that peptidoglycan-associated GAPDH recruits C1q from human serum but does not activate the complement pathway.
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