The staphylococcal elastin-binding protein regulates zinc-dependent growth/biofilm formation.
The staphylococcal elastin-binding protein regulates zinc-dependent growth/biofilm formation.
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DOI：
10.1093/jb/mvu027
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发表时间：
2014-09
影响因子：
2.7
通讯作者：
Makoto Nakakido;Chihiro Aikawa;I. Nakagawa;K. Tsumoto
中科院分区：
文献类型：
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作者：
Makoto Nakakido;Chihiro Aikawa;I. Nakagawa;K. Tsumoto
金黄色葡萄球菌是最重要的人类病原体之一，因为它是医院感染的常见原因。金黄色葡萄球菌的弹性蛋白结合蛋白（EbpS）是一种粘附素，负责通过其与弹性蛋白的结合而附着于宿主细胞。尽管它对粘附的贡献相对较弱，但ebpS基因在S.金黄色葡萄球菌分离株，这表明EbpS可能具有其他重要功能。在这里，我们发现EbpS结合Zn（2+）与其N-末端区域，这导致局部构象的变化，导致EbpS蛋白的组装。EbpS缺陷型菌株的生长速率显著降低。Zn（2+）螯合作用降低了野生型菌株的生长速率，但没有改变EbpS缺陷型菌株的生长速率。此外，EbpS缺陷型菌株的生物膜形成以Zn（2+）浓度依赖性方式异常增强。所有的结果表明，ebpS缺乏导致锌浓度依赖性无法适当地调节生长/生物膜成熟阶段。鉴于ebpS的高度保守性以及生物膜形成的适当调节被认为是有效的葡萄球菌感染所必需的，抑制EbpS与Zn（2+）的结合可能导致控制S的新治疗策略的发展。金黄色葡萄球菌感染。
Staphylococcus aureus is one of the most important human pathogens because it is a common cause of nosocomial infections. The elastin-binding protein of Staphylococcus aureus (EbpS) is an adhesin that is responsible for attachment to host cells via its binding to elastin. Despite its relatively weak contribution to adhesion, the ebpS gene is highly conserved among S. aureus isolates, suggesting that EbpS may have other crucial functions. Here, we found that EbpS binds Zn(2+) with its N-terminal region, which leads to local conformational changes that result in the assembly of the EbpS protein. The growth rate of the EbpS-deficient strain was considerably decreased. Zn(2+) chelation decreased the growth rate of the wild-type strain but did not alter that of the EbpS-deficient strain. Furthermore, biofilm formation by the EbpS-deficient strain was abnormally enhanced in the Zn(2+) concentration-dependent manner. All the results suggest that ebpS deficiency led to a zinc concentration-dependent inability to modulate the growth/biofilm maturation phase appropriately. Given the high conservation of ebpS and that appropriate regulation of biofilm formation is thought to be essential for effective staphylococcal infection, inhibition of EbpS binding to Zn(2+) could lead to the development of novel therapeutic strategies for controlling S. aureus infections.