Surface Coatings that Promote Rapid Release of Peptide-Based AgrC Inhibitors for Attenuation of Quorum Sensing in Staphylococcus aureus
Surface Coatings that Promote Rapid Release of Peptide-Based AgrC Inhibitors for Attenuation of Quorum Sensing in Staphylococcus aureus
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DOI：
10.1002/adhm.201300119
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发表时间：
2014-01-01
影响因子：
10
通讯作者：
Lynn, David M.
中科院分区：
文献类型：
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作者：
Broderick, Adam H.;Stacy, Danielle M.;Lynn, David M.
金黄色葡萄球菌是导致多种危及生命的感染的主要人类病原体。这种微生物的致病性归因于其产生一系列毒力因子和毒素的能力，包括超抗原中毒性休克综合征毒素-1（TSST-1）。虽然很多S。金黄色葡萄球菌感染可以使用常规抗生素治疗，已经出现了对这些杀菌剂具有抗性的菌株。通过非杀菌机制抑制致病性的方法（即，抗病毒方法）可以为治疗感染提供新的选择，包括由耐药菌株引起的感染。在这里，我们报告了一种非杀菌的方法来抑制致病性的基础上释放的大环肽（1和2），抑制agr群体感应（QS）电路在第三组S。金黄色。它表明，这些肽可以固定在平面和复杂的物体（载玻片上，非织造网，或吸收棉塞内）使用快速溶解的聚合物羧甲基纤维素（CMC）。当在III组S存在下孵育时，负载肽的CMC膜快速（95%）释放肽抑制agr QS回路，而不诱导细胞死亡。金黄色葡萄球菌GFP报告菌株。肽1是S.迄今为止报道的金黄色葡萄球菌中，III组QS回路调节TSST-1的产生，TSST-1是中毒性休克综合征（TSS）的主要原因。因此，这些结果提出了在临床和个人护理环境中处理棉塞、伤口敷料或其他物体的外覆盖物以抑制毒素产生并降低TSS严重性的方法。因为肽1也抑制S中的QS。金黄色葡萄球菌组-I、-II和-IV，该方法还可以在更广泛的背景下提供用于减弱QS和相关毒力表型的途径。
Staphylococcus aureus is a major human pathogen responsible for a variety of life-threatening infections. The pathogenicity of this organism is attributed to its ability to produce a range of virulence factors and toxins, including the superantigen toxic shock syndrome toxin-1 (TSST-1). While many S. aureus infections can be treated using conventional antibiotics, strains resistant to these bactericidal agents have emerged. Approaches that suppress pathogenicity through mechanisms that are nonbactericidal (i.e., antivirulence approaches) could provide new options for treating infections, including those caused by resistant strains. Here, we report a nonbactericidal approach to suppressing pathogenicity based on the release of macrocyclic peptides (1 and 2) that inhibit the agr quorum sensing (QS) circuit in group-III S. aureus. It is demonstrated that these peptides can be immobilized on planar and complex objects (on glass slides, nonwoven meshes, or within absorbent tampons) using the rapidly dissolving polymer carboxymethylcellulose (CMC). Peptide-loaded CMC films released peptide rapidly (95%) inhibition of the agr QS circuit without inducing cell death when incubated in the presence of a group-III S. aureus gfp-reporter strain. Peptide 1 is among the most potent inhibitors of QS in S. aureus reported to date, and the group-III QS circuit regulates production of TSST-1, the primary cause of toxic shock syndrome (TSS). These results thus suggest approaches to treat the outer covers of tampons, wound dressings, or other objects to suppress toxin production and reduce the severity of TSS in clinical and personal care contexts. Because peptide 1 also inhibits QS in S. aureus groups-I, -II, and -IV, this approach could also provide a pathway for attenuation of QS and associated virulence phenotypes in a broader range of contexts.