Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs.
Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs.
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DOI：
10.1517/17460441.2013.807245
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发表时间：
2013-09
影响因子：
6.3
通讯作者：
Lopez-Ribot JL
中科院分区：
文献类型：
--
作者：
Pierce CG;Lopez-Ribot JL
靶向致病机制而不是关键过程是开发新抗生素的一个非常有吸引力的选择。这在抗真菌药物方面可能尤其重要，因为迫切需要新的抗真菌药物，而且缺乏选择性的真菌靶标。条件致病真菌白色念珠菌是人类最常见的真菌感染--念珠菌病的主要病原体。这些感染的死亡率高得令人无法接受，这清楚地反映了当前抗真菌治疗的许多缺点，包括抗真菌药物的数量有限、毒性和出现耐药性。此外，抗真菌管道几乎是干的。该综述包括一些最新的进展，以了解白念珠菌的致病过程，以及如何利用这些信息来开发抗毒力药物。涉及的两个主要领域是丝化和生物膜形成，因为白色念珠菌的致病性与其在酵母和丝状形态之间进行形态转化的能力以及其形成生物膜的能力密切相关。我们认为，丝状化和生物被膜的形成代表了高价值的靶标，但在临床上尚未开发，用于开发新的抗毒力方法来对抗念珠菌病。尽管在分子水平上对白念珠菌毒力的了解越来越多，但这已被证明是一项艰巨的任务，但我们强调了针对这两个重要生物学过程的抗真菌药物开发的新机遇和前景。
Targeting pathogenetic mechanisms rather than essential processes represents a very attractive alternative for the development of new antibiotics. This may be particularly important in the case of antimycotics, due to the urgent need for novel antifungal drugs and the paucity of selective fungal targets. The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, the most common human fungal infection. These infections carry unacceptably high mortality rates, a clear reflection of the many shortcomings of current antifungal therapy, including the limited armamentarium of antifungal agents, their toxicity, and the emergence of resistance. Moreover the antifungal pipeline is mostly dry. This review covers some of the most recent progress towards understanding C. albicans pathogenetic processes and how to harness this information for the development of anti-virulence agents. The two principal areas covered are filamentation and biofilm formation, as C. albicans pathogenicity is intimately linked to its ability to undergo morphogenetic conversions between yeast and filamentous morphologies and to its ability to form biofilms. We argue that filamentation and biofilm formation represent high value targets, yet clinically unexploited, for the development of novel anti-virulence approaches against candidiasis. Although this has proved a difficult task despite increasing understanding at the molecular level of C. albicans virulence, we highlight new opportunities and prospects for antifungal drug development targeting these two important biological processes.
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DOI：
10.1038/nrmicro732
发表时间：
2003-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Casadevall A;Pirofski LA
通讯作者：
Pirofski LA
白色念珠菌基因组的人类策划注释。
影响因子：
4.5
作者：
Braun, BR;Hoog, MV;d'Enfert, C;Martchenko, M;Dungan, J;Kuo, A;Inglis, DO;Uhl, MA;Hogues, H;Berriman, M;Lorenz, M;Levitin, A;Oberholzer, U;Bachewich, C;Harcus, D;Marcil, A;Dignard, D;Iouk, T;Zito, R;Frangeul, L;Tekaia, F;Rutherford, K;Wang, E;Munro, CA;Bates, S;Gow, NA;Hoyer, LL;Köhler, G;Morschhäuser, J;Newport, G;Znaidi, S;Raymond, M;Turcotte, B;Sherlock, G;Costanzo, M;Ihmels, J;Berman, J;Sanglard, D;Agabian, N;Mitchell, AP;Johnson, AD;Whiteway, M;Nantel, A
通讯作者：
Nantel, A
影响因子：
3.7
作者：
Chang W;Li Y;Zhang L;Cheng A;Lou H
通讯作者：
Lou H
影响因子：
3.7
作者：
Chaturvedi AK;Lazzell AL;Saville SP;Wormley FL Jr;Monteagudo C;Lopez-Ribot JL
通讯作者：
Lopez-Ribot JL
影响因子：
11.4
作者：
Braun, BR;Kadosh, D;Johnson, AD
通讯作者：
Johnson, AD