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Antifungal Activity of 14-Helical β-Peptides against Planktonic Cells and Biofilms of Candida Species

机译:14螺旋β肽对念珠菌物种浮游细胞和生物膜的抗真菌活性。

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摘要

Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that β-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to β-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. β-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While β-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic β-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of β-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics.
机译:白色念珠菌是真菌感染的最普遍原因,并且由于耐药生物膜的形成(通常在植入的医疗设备的表面上),使治疗更加复杂。近年来,其他病原性念珠菌物种(如C. glabrata,C。parapsilosis和C.tropicis)真菌感染的发生率有所增加。天然抗菌性α肽的两亲性,螺旋β肽结构模拟物已显示出在体外对白色念珠菌具有特定的浮游抗真菌和抗生物膜形成活性。在这里,我们证明了β肽还具有抗临床分离的白色念珠菌耐药株和其他机会性念珠菌的功能。不同的念珠菌对β肽的敏感程度不同,其中热带念珠菌最易感染,而光滑念珠菌最不敏感。 β肽的疏水性与针对所有测试的念珠菌临床菌株和物种的抗真菌活性直接相关。尽管β肽在破坏现有的念珠菌生物膜方面非常无效,但疏水性β肽却能够阻止白色念珠菌,光滑念珠菌,副念珠菌和 C的形成。热带生物膜。 β肽对浮游细胞的广谱抗真菌活性以及在防止生物膜形成方面的潜力表明此类分子有望作为治疗剂。

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