A novel streptococcal cell-cell communication peptide promotes pneumococcal virulence and biofilm formation.
A novel streptococcal cell-cell communication peptide promotes pneumococcal virulence and biofilm formation.
复制标题
DOI：
10.1111/mmi.13721
复制
发表时间：
2017-08
影响因子：
3.6
通讯作者：
Hiller NL
中科院分区：
文献类型：
--
作者：
Cuevas RA;Eutsey R;Kadam A;West-Roberts JA;Woolford CA;Mitchell AP;Mason KM;Hiller NL
肺炎链球菌（肺炎球菌）是一种主要的人类病原体。它是人类呼吸道的常见殖民者，利用细胞间的通信系统来协调群体水平的行为。我们推断，感染期间高表达的分泌肽对于毒力至关重要。因此，我们使用计算机模式搜索来定义肺炎球菌分泌组，并分析了临床上重要的 PMEN1 谱系的转录组，以确定哪些肽编码基因在体内高表达。在这项研究中，我们鉴定了毒力肽 1 (vp1)，这是一种在龙猫中耳积液中高表达的 Gly-Gly 肽编码基因。 vp1 基因广泛分布于肺炎球菌中，并在相关物种中进行编码。对中耳感染龙猫模型的研究表明，VP1 是毒力决定因素。 vp1 基因受到 Rgg 家族转录因子及其同源 SHP（短疏水肽）的正向调节。体外数据表明，VP1 促进龙猫中耳上皮细胞上生长的生物膜厚度和生物量增加。此外，通过外源添加合成 VP1 可以恢复野生型生物膜。我们得出的结论是，VP1 是一种新型链球菌调节肽，可控制生物膜的发育和肺炎球菌的发病机制。肺炎链球菌无症状地定植于人类鼻咽部并传播至其他组织，导致轻度至重度疾病。它利用细胞间通信系统来协调群体水平的反应。然而，人们对这种细菌如何引起疾病知之甚少。我们描述了小肽 VP1 及其在临床相关肺炎球菌菌株生物膜发育和发病机制中的作用。我们的研究结果将揭示导致微生物毒力的生物过程。
Streptococcus pneumoniae (pneumococcus) is a major human pathogen. It is a common colonizer of the human respiratory track, where it utilizes cell-cell communication systems to coordinate population-level behaviors. We reasoned that secreted peptides that are highly expressed during infection are pivotal for virulence. Thus, we used in silico pattern searches to define a pneumococcal secretome, and analyzed the transcriptome of the clinically important PMEN1 lineage to identify which peptide-encoding genes are highly expressed in vivo. In this study, we characterized virulence peptide 1 (vp1), a highly expressed Gly-Gly peptide-encoding gene in chinchilla middle ear effusions. The vp1 gene is widely distributed across pneumococcus as well as encoded in related species. Studies in the chinchilla model of middle ear infection demonstrated that VP1 is a virulence determinant. The vp1 gene is positively regulated by a transcription factor from the Rgg family and its cognate SHP (short hydrophobic peptide). In vitro data indicated that VP1 promotes increased thickness and biomass for biofilms grown on chinchilla middle ear epithelial cells. Further, the wild-type biofilm is restored with the exogenous addition of synthetic VP1. We conclude that VP1 is a novel streptococcal regulatory peptide that controls biofilm development and pneumococcal pathogenesis. Streptococcus pneumoniae asymptomatically colonizes the human nasopharynx and disseminate to other tissues causing mild to severe disease. It utilizes cell-cell communication systems to coordinate population-level responses. However, how this bacteria cause disease is poorly understood. We describe the small peptide VP1 and its role in biofilm development and pathogenesis in a clinically relevant pneumococcal strain. Our findings will shed light on the biological processes that lead to microbial virulence.
登录
查看更多内容
影响因子：
6.4
作者：
Cook LC;LaSarre B;Federle MJ
通讯作者：
Federle MJ
影响因子：
4.8
作者：
Aggarwal, Chaitanya;Jimenez, Juan Cristobal;Federle, Michael J.
通讯作者：
Federle, Michael J.
影响因子：
4.8
作者：
den Hengst, CD;van Hijum, SAFT;Kuipers, OP
通讯作者：
Kuipers, OP
影响因子：
3.1
作者：
Dawid, Suzanne;Roche, Aoife M.;Weiser, Jeffrey N.
通讯作者：
Weiser, Jeffrey N.
影响因子：
3.7
作者：
Chang, Jennifer C.;Federle, Michael J.
通讯作者：
Federle, Michael J.