关键词: Staphylococcus aureus effector protein nuclease toxin pre-secretion complex type VII secretion system

Mesh : Humans Bacterial Proteins / genetics metabolism Type VII Secretion Systems / metabolism Staphylococcus aureus / genetics metabolism Gene Expression Regulation, Bacterial Toxins, Biological / metabolism

来  源:   DOI:10.1128/mbio.02100-23   PDF(Pubmed)

Abstract:
OBJECTIVE: Staphylococcus aureus is an opportunistic human pathogen associated with severe infections and antimicrobial resistance. S. aureus strains utilize a type VII secretion system to secrete toxins targeting competitor bacteria, likely facilitating colonization. EsaD is a nuclease toxin secreted by the type VII secretion system in many strains of S. aureus as well as other related bacterial species. Here, we identify three small proteins of previously unknown function as export factors, required for efficient secretion of EsaD. We show that these proteins bind to the transport domain of EsaD, forming a complex with a striking cane-like conformation.
摘要:
VIIb型分泌系统(T7SSb)是在革兰氏阳性芽孢杆菌中发现的多亚基蛋白出口机器,在细菌间竞争中起关键作用。T7SSb分泌多种靶向密切相关菌株的毒性效应蛋白;然而,T7SSb基因簇中许多保守基因的分泌机制和作用仍然未知。EsaD是金黄色葡萄球菌T7SSb分泌的核酸酶毒素,与其同源免疫蛋白形成分泌前复合物,EsaG,和陪护EsaE.EsaD的上游编码是三种功能未知的小分泌蛋白:EsxB,EsxC,和EsxD。这里,我们表明这三种蛋白质与EsaD结合并充当EsaD输出因子,并且我们报告了完整的T7SSb底物分泌前复合物的初步结构信息。EsaDEG三聚体和EsaDEG-EsxBCD六聚体的低温电子显微镜显示,EsxBCD的掺入赋予了细长的构象,该构象包含附着在长的窄轴上的柔性球状货物结构域,这对于有效的毒素输出至关重要。重要性金黄色葡萄球菌是一种机会性人类病原体,与严重感染和抗微生物药物耐药性有关。金黄色葡萄球菌菌株利用VII型分泌系统来分泌靶向竞争细菌的毒素,可能促进殖民。EsaD是由许多金黄色葡萄球菌菌株以及其他相关细菌物种中的VII型分泌系统分泌的核酸酶毒素。这里,我们确定了三种以前未知功能的小蛋白作为输出因子,有效分泌EsaD所需。我们发现这些蛋白质与EsaD的转运域结合,形成一个具有惊人的甘蔗状构象的复合体。
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