A C. elegans-based, whole animal, in vivo screen for the identification of antifungal compounds

被引:59
作者
Tampakakis, Emmanouil [1 ]
Okoli, Ikechukwu [1 ]
Mylonakis, Eleftherios [1 ]
机构
[1] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA
关键词
D O I
10.1038/nprot.2008.193
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Traditional antimicrobial screens focus on compounds that block the growth of microbial organisms. A new Caenorhabditis elegans-based bioassay can be used for the identification of antifungal compounds that are effective against Candida albicans. According to the protocol, adult nematodes are infected with C. albicans and moved to 96-well plates containing the tested compounds. In the presence of compounds with no antifungal activity, the fungus kills the worms and develops filaments that penetrate through the cuticle. In contrast to traditional screening methods and mammalian models, this facile, time-efficient and less costly assay allows the study of Candida cells in nonplanktonic form and may allow the concurrent evaluation of toxicity and antifungal activity and identify compounds that target virulence factors or modify host immune response. The screening assay takes about 5-6 d depending on the experimental design.
引用
收藏
页码:1925 / 1931
页数:7
相关论文
共 27 条
[11]  
Darby Creg, 2005, WormBook, P1
[12]   Candida biofilms and their role in infection [J].
Douglas, LJ .
TRENDS IN MICROBIOLOGY, 2003, 11 (01) :30-36
[13]   Finding function in novel targets:: C-elegans as a model organism [J].
Kaletta, T ;
Hengartner, MO .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (05) :387-398
[14]   A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity [J].
Kim, DH ;
Feinbaum, R ;
Alloing, G ;
Emerson, FE ;
Garsin, DA ;
Inoue, H ;
Tanaka-Hino, M ;
Hisamoto, N ;
Matsumoto, K ;
Tan, MW ;
Ausubel, FM .
SCIENCE, 2002, 297 (5581) :623-626
[15]   Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence [J].
Kumamoto, CA ;
Vinces, MD .
CELLULAR MICROBIOLOGY, 2005, 7 (11) :1546-1554
[16]   Infection in a dish: high-throughput analyses of bacterial pathogenesis [J].
Kurz, C. Leopold ;
Ewbank, Jonathan J. .
CURRENT OPINION IN MICROBIOLOGY, 2007, 10 (01) :10-16
[17]   Nonfilamentous C-albicans mutants are avirulent [J].
Lo, HJ ;
Kohler, JR ;
DiDomenico, B ;
Loebenberg, D ;
Cacciapuoti, A ;
Fink, GR .
CELL, 1997, 90 (05) :939-949
[18]   Identification of novel antimicrobials using a live-animal infection model [J].
Moy, Terence I. ;
Ball, Anthony R. ;
Anklesaria, Zafia ;
Casadei, Gabriele ;
Lewis, Kim ;
Ausubel, Frederick M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (27) :10414-10419
[19]   Worms and flies as genetically tractable animal models to study host-pathogen interactions [J].
Mylonakis, E ;
Aballay, A .
INFECTION AND IMMUNITY, 2005, 73 (07) :3833-3841
[20]   Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi [J].
Mylonakis, Eleftherios ;
Casadevall, Arturo ;
Ausubel, Frederick M. .
PLOS PATHOGENS, 2007, 3 (07) :859-865