The Quorum Sensing Inhibitor Hamamelitannin Increases Antibiotic Susceptibility of Staphylococcus aureus Biofilms by Affecting Peptidoglycan Biosynthesis and eDNA Release.
The Quorum Sensing Inhibitor Hamamelitannin Increases Antibiotic Susceptibility of Staphylococcus aureus Biofilms by Affecting Peptidoglycan Biosynthesis and eDNA Release.
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DOI：
10.1038/srep20321
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发表时间：
2016-02-01
影响因子：
4.6
通讯作者：
Coenye T
中科院分区：
文献类型：
--
作者：
Brackman G;Breyne K;De Rycke R;Vermote A;Van Nieuwerburgh F;Meyer E;Van Calenbergh S;Coenye T
由于耐甲氧西林菌株的快速出现和传播，金黄色葡萄球菌感染的治疗变得越来越具有挑战性。此外，S.金黄色葡萄球菌存在于感染部位的生物膜内。近年来，很少有新的抗菌剂被开发出来，它们的抑菌或杀菌活性导致选择压力，不可避免地诱导抗菌剂耐药性。因此，迫切需要具有其他作用模式的创新抗菌剂。一种替代方法是靶向细菌群体感应（QS）系统。金缕梅单宁（2′，5-二-O-没食子酰-d-金缕梅糖; HAM）以前被认为通过TraP QS系统阻断QS，并显示增加S。金黄色葡萄球菌生物膜对万古霉素（货车）的敏感性，尽管仍然缺乏机制见解。在本研究中，我们提供的证据表明，HAM特别影响S。通过影响S. aureus的细胞壁合成和胞外DNA释放，通过TraP受体对S. aureus生物膜的易感性产生影响。金黄色。我们进一步提供了HAM可以增加S.金黄色葡萄球菌生物膜对不同类别的抗生素在体外。最后，我们表明，HAM增加S的易感性。金黄色葡萄球菌对体内秀丽隐杆线虫和小鼠乳腺感染模型中抗生素治疗的影响。
Treatment of Staphylococcus aureus infections has become increasingly challenging due to the rapid emergence and dissemination of methicillin-resistant strains. In addition, S. aureus reside within biofilms at the site of infection. Few novel antibacterial agents have been developed in recent years and their bacteriostatic or bactericidal activity results in selective pressure, inevitably inducing antimicrobial resistance. Consequently, innovative antimicrobials with other modes of action are urgently needed. One alternative approach is targeting the bacterial quorum sensing (QS) system. Hamamelitannin (2′,5-di-O-galloyl-d-hamamelose; HAM) was previously suggested to block QS through the TraP QS system and was shown to increase S. aureus biofilm susceptibility towards vancomycin (VAN) although mechanistic insights are still lacking. In the present study we provide evidence that HAM specifically affects S. aureus biofilm susceptibility through the TraP receptor by affecting cell wall synthesis and extracellular DNA release of S. aureus. We further provide evidence that HAM can increase the susceptibility of S. aureus biofilms towards different classes of antibiotics in vitro. Finally, we show that HAM increases the susceptibility of S. aureus to antibiotic treatment in in vivo Caenorhabditis elegans and mouse mammary gland infection models.