Furanone at Subinhibitory Concentrations Enhances Staphylococcal Biofilm Formation by luxS Repression
Furanone at Subinhibitory Concentrations Enhances Staphylococcal Biofilm Formation by luxS Repression
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DOI：
10.1128/aac.01704-08
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发表时间：
2009-10-01
影响因子：
4.9
通讯作者：
Landmann, Regine
中科院分区：
文献类型：
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作者：
Kuehl, Richard;Al-Bataineh, Sameer;Landmann, Regine
溴代呋喃酮对革兰氏阴性菌的生物膜形成和群体感应等多细胞行为有抑制作用，但不影响其生长。呋喃酮与QS在革兰氏阳性菌中的相互作用尚不清楚。葡萄球菌有两个QS系统，agr和luxS，分别通过两种不同的途径降低生物膜形成，RNAIII上调和细菌分离，以及多糖细胞间粘附素（PIA）减少。我们合成了天然呋喃酮化合物2 [（5 Z）-4-溴-5-（溴亚甲基）-3-丁基-2（5 H）-呋喃酮]和3个类似物，研究它们对革兰氏阳性菌生物膜形成的影响。化合物2，而不是类似物，增强了表皮葡萄球菌1457和047以及S.金黄色葡萄球菌纽曼，浓度在1.25和20 μ M之间。结果表明，S.表皮葡萄球菌和表皮葡萄球菌。金黄色葡萄球菌通过游离呋喃酮，并显示杀菌活性。在MIC的10%至20%的浓度下发生生物膜的诱导，并与PIA的增加相关。生物膜效应是agr独立的。这是由于对luxS的干扰，如在化合物2存在下luxS表达降低和在添加呋喃酮后luxS突变体中不依赖强生物膜形成所示。聚（L-赖氨酸）接枝/聚（乙二醇）接枝呋喃酮对生物膜无效，不杀菌，表明游离呋喃酮的必要性。游离呋喃酮对鼠成纤维细胞的毒性与对葡萄球菌的毒性相似，不包括该化合物的治疗应用。总之，我们观察到葡萄球菌中呋喃酮在亚抑制浓度下的生物膜增强，其表现为PIA增加并依赖于luxS。
Brominated furanones from marine algae inhibit multicellular behaviors of gram-negative bacteria such as biofilm formation and quorum sensing (QS) without affecting their growth. The interaction of furanone with QS in gram-positive bacteria is unknown. Staphylococci have two QS systems, agr and luxS, which lower biofilm formation by two different pathways, RNAIII upregulation and bacterial detachment, and polysaccharide intercellular adhesin ( PIA) reduction, respectively. We synthesized natural furanone compound 2 [(5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone] from Delisea pulchra and three analogues to investigate their effect on biofilm formation in gram-positive bacteria. Compound 2, but not the analogues, enhanced the biofilms of Staphylococcus epidermidis 1457 and 047 and of S. aureus Newman at concentrations between 1.25 and 20 mu M. We show the growth inhibition of S. epidermidis and S. aureus by free furanone and demonstrate bactericidal activity. An induction of biofilm occurred at concentrations of 10 to 20% of the MIC and correlated with an increase in PIA. The biofilm effect was agr independent. It was due to interference with luxS, as shown by reduced luxS expression in the presence of compound 2 and independence of the strong biofilm formation in a luxS mutant upon furanone addition. Poly(L-lysine)-grafted/poly(ethylene glycol)-grafted furanone was ineffective on biofilm and not bactericidal, indicating the necessity for free furanone. Free furanone was similarly toxic for murine fibroblasts as for staphylococci, excluding a therapeutic application of this compound. In summary, we observed a biofilm enhancement by furanone in staphylococci at subinhibitory concentrations, which was manifested by an increase in PIA and dependent on luxS.