Functional amyloids composed of phenol soluble modulins stabilize Staphylococcus aureus biofilms.

Functional amyloids composed of phenol soluble modulins stabilize Staphylococcus aureus biofilms.
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DOI:
10.1371/journal.ppat.1002744
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发表时间:
2012
期刊:
影响因子:
6.7
通讯作者:
Boles BR
Boles BR
中科院分区:
医学1区
文献类型:
--
作者:
Schwartz K;Syed AK;Stephenson RE;Rickard AH;Boles BR

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金黄色葡萄球菌是一种机会性病原体,定植在哺乳动物的皮肤和粘膜表面。持续性葡萄球菌感染通常涉及称为生物膜的表面相关群落。在这里,我们报告发现一种新的细胞外纤维结构,促进金黄色葡萄球菌生物膜的完整性。生化和遗传分析表明,这些纤维具有淀粉样蛋白的特性,由称为酚溶性调节素(psm)的小肽组成。不能产生psm的突变体容易受到基质降解酶和机械应力的破坏。先前的研究已经将PSM与生物膜的分解联系起来,我们提出的数据表明,可溶性PSM肽分散生物膜,而聚合肽则不会。这项工作表明psm聚集成淀粉样纤维调节了它们的生物活性和在生物膜中的作用。大多数人都知道金黄色葡萄球菌是一种高度传染性的“超级细菌”,但许多人并不知道金黄色葡萄球菌在鼻子和其他身体壁龛中是非传染性的。目前尚不清楚金黄色葡萄球菌如何以及为什么能够在宿主体内适应并容易地在共生和致病生活方式之间切换;然而,积聚成多细胞聚集体的能力是两种生活方式的标志。在这项工作中,我们证明了金黄色葡萄球菌在多细胞生物膜群落中产生细胞外纤维,这些纤维帮助细菌群落承受物理压力。令人惊讶的是,这些纤维由被称为酚溶性调节素(psm)的小肽组成,这种小肽先前被认为与生物膜分解和毒性有关。我们证明PSM肽在纤维中的积累调节了它们分散生物膜的能力。因此,psm完成由淀粉样蛋白聚集调节的双重和相反的作用。葡萄球菌从未被证明产生这种细胞外结构,我们的发现可能对我们对金黄色葡萄球菌生理学的理解产生深远的影响。我们发现这些结构是由已知的毒力因子组成的,这表明了体内传染性和静态生活方式之间的共同途径。
Staphylococcus aureus is an opportunistic pathogen that colonizes the skin and mucosal surfaces of mammals. Persistent staphylococcal infections often involve surface-associated communities called biofilms. Here we report the discovery of a novel extracellular fibril structure that promotes S. aureus biofilm integrity. Biochemical and genetic analysis has revealed that these fibers have amyloid-like properties and consist of small peptides called phenol soluble modulins (PSMs). Mutants unable to produce PSMs were susceptible to biofilm disassembly by matrix degrading enzymes and mechanical stress. Previous work has associated PSMs with biofilm disassembly, and we present data showing that soluble PSM peptides disperse biofilms while polymerized peptides do not. This work suggests the PSMs' aggregation into amyloid fibers modulates their biological activity and role in biofilms. Most people know Staphylococcus aureus as a highly infectious “Super Bug”, but many are not aware that S. aureus non-infectiously colonizes much of the population in the nose, among other bodily niches. It is not well understood how and why S. aureus is able to adapt and readily switch between the commensal and pathogenic lifestyle within the host; however, the capacity to accumulate into multicellular aggregates is a hallmark associated with both lifestyles. In this work, we demonstrate that S. aureus produces extracellular fibers in multicellular biofilm communities, and that these fibers help the bacterial community to withstand physical stresses. Surprisingly, these fibers consist of small peptides called phenol soluble modulins (PSMs) that have previously been implicated in biofilm disassembly and virulence. We demonstrate that accumulation of PSM peptides into fibers modulates their ability to disperse biofilms. Thus, PSMs fulfill dual and opposing roles that are modulated by amyloid-like aggregation. Staphylococci have never before been shown to produce this kind of extracellular structure, and our findings may have a profound impact on our understanding of S. aureus physiology. We have found that these structures are composed of known virulence factors, which indicates a common pathway between infectious and static lifestyles in the body.
DOI: 10.1016/j.bbapap.2010.04.001
发表时间: 2010-07
期刊: Biochimica et biophysica acta
影响因子: --
作者:
Biancalana M;Koide S
通讯作者: Koide S
DOI: 10.1007/bf00259623
发表时间: 1989-11-01
期刊: MOLECULAR AND GENERAL GENETICS
影响因子: --
作者:
JANZON, L;LOFDAHL, S;ARVIDSON, S
通讯作者: ARVIDSON, S
DOI: 10.1371/journal.pone.0008557
发表时间: 2010-01-05
期刊: PloS one
影响因子: 3.7
作者:
Cogen AL;Yamasaki K;Muto J;Sanchez KM;Crotty Alexander L;Tanios J;Lai Y;Kim JE;Nizet V;Gallo RL
通讯作者: Gallo RL
DOI: 10.1111/j.1365-2958.2009.06838.x
发表时间: 2009-09-01
影响因子: 3.6
作者:
de Jong, Wouter;Wosten, Han A. B.;Claessen, Dennis
通讯作者: Claessen, Dennis