The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner.
The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner.
复制标题
阿司匹林的活性成分，水杨酸，以PIA依赖性方式促进金黄色葡萄球菌生物膜形成。
DOI：
10.3389/fmicb.2017.00004
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发表时间：
2017
影响因子：
5.2
通讯作者：
Buzzola FR
中科院分区：
文献类型：
--
作者：
Dotto C;Lombarte Serrat A;Cattelan N;Barbagelata MS;Yantorno OM;Sordelli DO;Ehling-Schulz M;Grunert T;Buzzola FR
阿司匹林对人体健康有明显的益处。但是水杨酸（SAL）-阿司匹林的主要生物代谢物-对真核生物和原核生物细胞有几种作用。SAL可以影响例如金黄色葡萄球菌毒力因子的表达。SAL还可以与铁离子形成络合物，并且已经表明不同的铁螯合分子减少了S的形成。金黄色葡萄球菌生物膜。本研究的目的是阐明SAL引起的铁含量限制是否可以改变S。金黄色葡萄球菌代谢和/或代谢调节剂，从而改变参与生物膜形成的主要多糖的表达。与对照组相比，暴露于2 mM SAL的生物膜诱导细胞内游离Fe 2+浓度降低27%。此外，SAL耗尽培养基中23%的可用游离Fe 2+阳离子。这些温和的铁限制条件促进了菌株纽曼和S.与USA300和USA100克隆相关的金黄色葡萄球菌临床分离株。SAL引起的铁生物利用度的轻微降低足以诱导甲氧西林耐药和敏感的S.金黄色葡萄球菌S.当金黄色葡萄球菌在任何测试的实验条件下形成生物膜时，其不产生荚膜多糖（CP）。此外，SAL降低乌头酸酶活性，刺激乳酸发酵途径形成生物膜的细菌。S.检测金黄色葡萄球菌生物膜，FTIR光谱分析显示SAL以codY依赖性方式产生明显影响。此外，SAL对成熟生物膜中的codY转录产生负面影响，从而缓解ica操纵子的CodY阻遏。用SAL处理小鼠诱导金黄色葡萄球菌定殖的显著增加。提示SAL诱导的PIA表达升高可能是导致小鼠鼻腔定植的原因。SAL诱导的生物膜可能有助于S.金黄色葡萄球菌感染在素食者以及经常服用阿司匹林的患者中持续存在。
Aspirin has provided clear benefits to human health. But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. SAL can affect, for instance, the expression of Staphylococcus aureus virulence factors. SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. S. aureus did not produce capsular polysaccharide (CP) when it was forming biofilms under any of the experimental conditions tested. Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. Treatment of mice with SAL induced a significant increase of S aureus colonization. It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. SAL-induced biofilms may contribute to S. aureus infection persistence in vegetarian individuals as well as in patients that frequently consume aspirin.