Aryl-Alkyl-Lysines: Agents That Kill Planktonic Cells, Persister Cells, Biofilms of MRSA and Protect Mice from Skin-Infection.
Aryl-Alkyl-Lysines: Agents That Kill Planktonic Cells, Persister Cells, Biofilms of MRSA and Protect Mice from Skin-Infection.
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DOI：
10.1371/journal.pone.0144094
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Haldar J
中科院分区：
文献类型：
--
作者：
Ghosh C;Manjunath GB;Konai MM;Uppu DS;Hoque J;Paramanandham K;Shome BR;Haldar J
开发对抗葡萄球菌感染的合成策略，特别是由耐甲氧西林金黄色葡萄球菌（MRSA）引起的葡萄球菌感染，需要立即予以关注。在这篇文章中，我们报道了芳基烷基赖氨酸这种简单的膜活性小分子对MRSA浮游细胞、持久性细胞和生物膜引起的感染的治疗能力。一种具有代表性的化合物NCK-10在多次传代中没有诱导浮游细胞产生抗性，并且在不同的pH和盐度环境中保持活性。在低浓度下，该化合物能够快速地去极化和渗透金黄色葡萄球菌的细胞膜。用该化合物处理不仅可以根除预先形成的MRSA生物膜，还可以降低细菌生物膜的活菌数。在MRSA皮肤感染的小鼠模型中，该化合物在降低细菌负担方面比夫西地酸更有效。总的来说，这类分子具有作为抗皮肤感染的抗菌剂的潜力。
Development of synthetic strategies to combat Staphylococcal infections, especially those caused by methicillin resistant Staphyloccus aureus (MRSA), needs immediate attention. In this manuscript we report the ability of aryl-alkyl-lysines, simple membrane active small molecules, to treat infections caused by planktonic cells, persister cells and biofilms of MRSA. A representative compound, NCK-10, did not induce development of resistance in planktonic cells in multiple passages and retained activity in varying environments of pH and salinity. At low concentrations the compound was able to depolarize and permeabilize the membranes of S. aureus persister cells rapidly. Treatment with the compound not only eradicated pre-formed MRSA biofilms, but also brought down viable counts in bacterial biofilms. In a murine model of MRSA skin infection, the compound was more effective than fusidic acid in bringing down the bacterial burden. Overall, this class of molecules bears potential as antibacterial agents against skin-infections.