Activity of antimicrobial peptide mimetics in the oral cavity: I. Activity against biofilms of Candida albicans
Activity of antimicrobial peptide mimetics in the oral cavity: I. Activity against biofilms of Candida albicans
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DOI：
10.1111/j.2041-1014.2010.00590.x
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发表时间：
2010-12-01
影响因子：
3.7
通讯作者：
Diamond, G.
中科院分区：
文献类型：
--
作者：
Hua, J.;Yamarthy, R.;Diamond, G.
天然产生的抗菌肽有望成为治疗口腔白色念珠菌等病原体的药物，但许多困难减缓了它们的发展。模拟这些多肽性质的人工合成的非肽类似物具有许多优点，并显示出强大的、选择性的抗菌活性。开发了几个系列的模拟物(分子量为1000)，并对口腔念珠菌菌株进行了筛选，作为其抗真菌特性的原则证明。一种苯乙炔和几种降低哺乳动物细胞毒性的芳酰胺化合物被发现对白色念珠菌有活性。这些化合物在液体培养中表现出快速的杀菌活性，即使在唾液存在的情况下也是如此，并显示出与标准抗真菌药物的协同作用。当对生长在假牙丙烯酸上的生物膜进行测试时，通过代谢和荧光活性测试表明，这些化合物具有很强的杀菌活性。与氟康唑不同，在亚最低抑菌浓度水平下重复传代不会导致念珠菌耐药。我们的结果证明了这些化合物用作抗念珠菌药物的原理证明，它们的进一步测试作为新的抗念珠菌疗法是有必要的。
P>Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans but numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (with molecular weight < 1000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-minimum inhibitory concentration levels did not lead to resistant Candida, in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.