Oligomerization of RNAIII-Inhibiting Peptide Inhibits Adherence and Biofilm Formation of Methicillin-Resistant Staphylococcus aureus In Vitro and In Vivo
Oligomerization of RNAIII-Inhibiting Peptide Inhibits Adherence and Biofilm Formation of Methicillin-Resistant Staphylococcus aureus In Vitro and In Vivo
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RNAIII 抑制肽的寡聚化在体外和体内抑制耐甲氧西林金黄色葡萄球菌的粘附和生物膜形成
DOI：
10.1089/mdr.2015.0170
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发表时间：
2016
影响因子：
2.6
通讯作者：
Hou Zheng
中科院分区：
文献类型：
--
作者：
Zhou Ying;Zhao Ruzhou;Ma Bo;Gao Han;Xue Xiaoyan;Qu Di;Li Mingkai;Meng Jingru;Luo Xiaoxing;Hou Zheng
生物膜的形成增强了细菌的耐药性，使治疗复杂化。因此，迫切需要一种治疗金黄色葡萄球菌生物膜感染性疾病的创新策略. RNA Ⅲ抑制肽（RIP）是一种群体感应抑制剂，金黄色生物膜形成。然而，RIP单独使用或低剂量使用时，其抗氧化膜活性较差。RIP的活性和稳定性可以通过氨基酸取代、末端修饰或寡聚化来设计其衍生物来增强。其中，16 P-AC显著降低了耐甲氧西林菌的生物膜形成和粘附。通过抑制4种生物膜形成相关基因的表达水平，体外培养金黄色葡萄球菌（MRSA）。此外，16 P-AC通过降低尿液、肾脏、支架和膀胱中的细菌滴度以及通过抑制植入支架上的细胞间粘附，在MRSA诱导的大鼠尿路感染模型中显示出优异的保护作用。该衍生物在大鼠血浆中也表现出相对良好的稳定性。因此，16 P-AC是治疗MRSA引起的生物膜相关感染的潜在候选药物。该修饰策略对提高RIP在体内的代谢稳定性和活性是可行的。
Biofilm formation enhances bacterial resistance and complicates treatment. Therefore, an innovative strategy is urgently needed for the treatment ofStaphylococcus aureusbiofilm infectious diseases. RNAIII-inhibiting peptide (RIP), as a quorum-sensing inhibitor, inhibitsS. aureusbiofilm formation. However, RIP possesses poor antibiofilm activity when used alone or at a low dosein vivo. The activity and stability of RIP can be enhanced by designing its derivatives through amino acid substitution, terminal modification, or oligomerization. Among the derivatives, 16P-AC significantly decreased the biofilm formation and adherence of methicillin-resistantS. aureus(MRSA) on polystyrene material by inhibiting the expression level of four biofilm formation-related genesin vitro. Moreover, 16P-AC showed excellent protective effects by decreasing the bacterial titers in the urine, kidney, stent, and bladder, as well as by inhibiting intercellular adhesion on the implanted stent, in a rat urinary tract infection model induced by MRSA. This derivative also exhibited a relatively good stability in rat plasma. Therefore, 16P-AC is a potential drug candidate to treat biofilm-associated infections caused by MRSA. The present modification strategy is feasible to improve the metabolic stability and activity of RIPin vivo.