Small-molecule inhibitors of biofilm formation in laboratory and clinical isolates of Candida albicans
Small-molecule inhibitors of biofilm formation in laboratory and clinical isolates of Candida albicans
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DOI：
10.1099/jmm.0.034124-0
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发表时间：
2012-01-01
影响因子：
3
通讯作者：
Johnson, Douglas I.
中科院分区：
文献类型：
--
作者：
Grald, Ariel;Yargosz, Philip;Johnson, Douglas I.
白色念珠菌细胞能够在生物和非生物表面（例如留置医疗器械）上形成生物膜。白色念珠菌细胞可以在芽生和菌丝生长形式之间相互转化，本文称为芽生到菌丝转变（BHT），这对于成熟生物膜的形成很重要。之前的工作鉴定了 23 种有机小分子，它们可以抑制 BHT，但不会影响白色念珠菌细胞活力或出芽细胞生长。这些 BHT 抑制剂被认为可以抑制调节 BHT 的多种信号通路，其中许多信号通路还调节生物膜的形成。然而，只有三种 BHT 抑制剂：buhytrinA、ETYA 和 CGP-37157 能够抑制野生型实验室白色念珠菌菌株的体外生物膜形成。当检查临床白色念珠菌分离株形成生物膜的能力时，测试的 28 个临床分离株中只有 11 个（39%）能够形成生物膜。虽然buhytrinA、ETYA和CGP-37157可以抑制所有28个临床分离株的BHT，但它们只能抑制这些临床分离株的子集的生物膜形成，其中ETYA具有100%的功效。这些数据表明白色念珠菌实验室和临床分离株的生物膜形成能力以及 BHT 抑制剂针对这些不同分离株的功效可能存在显着差异。在检查潜在的新抗真菌疗法时，实验室和临床分离株之间的这些差异应该是需要考虑的一个重要方面。
Candida albicans cells have the ability to form biofilms on biotic and abiotic surfaces, such as indwelling medical devices. C. albicans cells can interconvert between budded and hyphal growth forms, herein termed the budded-to-hyphal transition (BHT), which is important for the formation of mature biofilms. Previous work identified 23 small organic molecules that could inhibit the BHT but did not affect C. albicans cell viability or budded cell growth. These BHT inhibitors were proposed to inhibit multiple signalling pathways regulating the BHT, many of which also regulate biofilm formation. However, only three of the BHT inhibitors, buhytrinA, ETYA and CGP-37157, were capable of inhibiting in vitro biofilm formation of wild-type laboratory C. albicans strains. When clinical C. albicans isolates were examined for their ability to form biofilms, only 11 of the 28 clinical isolates tested (39%) were capable of forming biofilms. Although buhytrinA, ETYA and CGP-37157 could inhibit the BHT of all 28 clinical isolates, they were only able to inhibit biofilm formation of a subset of these clinical isolates, with ETYA having 100% efficacy. These data indicate that the biofilm-forming capability of laboratory and clinical isolates of C. albicans, as well as the efficacy of BHT inhibitors against these different isolates, can differ dramatically. These differences between laboratory and clinical isolates should be an important aspect to consider when examining potentially new antifungal therapeutics.