Using Caenorhabditis elegans for antimicrobial drug discovery

被引:31
作者
Desalermos, Athanasios [1 ]
Muhammed, Maged [1 ]
Glavis-Bloom, Justin [1 ]
Mylonakis, Eleftherios [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA
关键词
Caenorhabditis elegans; Candida albicans; drug discovery; high throughput; model host; THROUGHPUT SCREENING ASSAYS; HOST-PATHOGEN INTERACTIONS; ANIMAL INFECTION MODEL; CRYPTOCOCCUS-NEOFORMANS; C-ELEGANS; CANDIDA-ALBICANS; INNATE IMMUNITY; ACINETOBACTER-BAUMANNII; ANTIFUNGAL COMPOUNDS; ALZHEIMERS-DISEASE;
D O I
10.1517/17460441.2011.573781
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: The number of microorganism strains with resistance to known antimicrobials is increasing. Therefore, there is a high demand for new, nontoxic and efficient antimicrobial agents. Research with the microscopic nematode Caenorhabditis elegans can address this high demand for the discovery of new antimicrobial compounds. In particular, C. elegans can be used as a model host for in vivo drug discovery through high-throughput screens of chemical libraries. Areas covered: This review introduces the use of substitute model hosts and especially C. elegans in the study of microbial pathogenesis. The authors also highlight recently published literature on the role of C. elegans in drug discovery and outline its use as a promising host with unique advantages in the discovery of new antimicrobial drugs. Expert opinion: Caenorhabditis elegans can be used, as a model host, to research many diseases, including fungal infections and Alzheimer's disease. In addition, high-throughput techniques for screening chemical libraries can also be facilitated. Nevertheless, C. elegans and mammals have significant differences that both limit the use of the nematode in research and the degree by which results can be interpreted. That being said, the use of C. elegans in drug discovery still holds promise and the field continues to grow, with attempts to improve the methodology already underway.
引用
收藏
页码:645 / 652
页数:8
相关论文
共 93 条
[71]   Candida albicans Hyphal Formation and Virulence Assessed Using a Caenorhabditis elegans Infection Model [J].
Pukkila-Worley, Read ;
Peleg, Anton Y. ;
Tampakakis, Emmanouil ;
Mylonakis, Eleftherios .
EUKARYOTIC CELL, 2009, 8 (11) :1750-1758
[72]   Protein Kinase D Is an Essential Regulator of C. elegans Innate Immunity [J].
Ren, Min ;
Feng, Hui ;
Fu, Ya ;
Land, Marianne ;
Rubin, Charles S. .
IMMUNITY, 2009, 30 (04) :521-532
[73]   The impact of candidemia on length of hospital stay, outcome, and overall cost of illness [J].
Rentz, AM ;
Halpern, MT ;
Bowden, R .
CLINICAL INFECTIOUS DISEASES, 1998, 27 (04) :781-788
[74]   WormBase 2007 [J].
Rogers, Anthony ;
Antoshechkin, Igor ;
Bieri, Tamberlyn ;
Blasiar, Darin ;
Bastiani, Carol ;
Canaran, Payan ;
Chan, Juancarlos ;
Chen, Wen J. ;
Davis, Paul ;
Fernandes, Jolene ;
Fiedler, Tristan J. ;
Han, Michael ;
Harris, Todd W. ;
Kishore, Ranjana ;
Lee, Raymond ;
Mckay, Sheldon ;
Mueller, Hans-Michael ;
Nakamura, Cecilia ;
Ozersky, Philip ;
Petcherski, Andrei ;
Schindelman, Gary ;
Schwarz, Erich M. ;
Spooner, Will ;
Tuli, Mary Ann ;
Van Auken, Kimberly ;
Wang, Daniel ;
Wang, Xiaodong ;
Williams, Gary ;
Yook, Karen ;
Durbin, Richard ;
Stein, Lincoln D. ;
Spieth, John ;
Sternberg, Paul W. .
NUCLEIC ACIDS RESEARCH, 2008, 36 :D612-D617
[75]   Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model [J].
Santangelo, R ;
Zoellner, H ;
Sorrell, T ;
Wilson, C ;
Donald, C ;
Djordjevic, J ;
Shounan, Y ;
Wright, L .
INFECTION AND IMMUNITY, 2004, 72 (04) :2229-2239
[76]   Inhibition of filamentation can be used to treat disseminated candidiasis [J].
Saville, Stephen P. ;
Lazzell, Anna L. ;
Bryant, Alexander P. ;
Fretzen, Angelika ;
Monreal, Alex ;
Solberg, Erik O. ;
Monteagudo, Carlos ;
Lopez-Ribot, Jose L. ;
Milne, G. Todd .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2006, 50 (10) :3312-3316
[77]   C-elegans as Model for the Study of High Glucose-Mediated Life Span Reduction [J].
Schlotterer, Andreas ;
Kukudov, Georgi ;
Bozorgmehr, Farastuk ;
Hutter, Harald ;
Du, Xueliang ;
Oikonomou, Dimitrios ;
Ibrahim, Youssef ;
Pfisterer, Friederike ;
Rabbani, Naila ;
Thornalley, Paul ;
Sayed, Ahmed ;
Fleming, Thomas ;
Humpert, Per ;
Schwenger, Vedat ;
Zeier, Martin ;
Hamann, Andreas ;
Stern, David ;
Brownlee, Michael ;
Bierhaus, Angelika ;
Nawroth, Peter ;
Morcos, Michael .
DIABETES, 2009, 58 (11) :2450-2456
[78]   WormBase:: better software, richer content [J].
Schwarz, Erich M. ;
Antoshechkin, Igor ;
Bastiani, Carol ;
Bieri, Tamberlyn ;
Blasiar, Darin ;
Canaran, Payan ;
Chan, Juancarlos ;
Chen, Nansheng ;
Chen, Wen J. ;
Davis, Paul ;
Fiedler, Tristan J. ;
Girard, Lisa ;
Harris, Todd W. ;
Kenny, Eimear E. ;
Kishore, Ranjana ;
Lawson, Dan ;
Lee, Raymond ;
Mueller, Hans-Michael ;
Nakamura, Cecilia ;
Ozersky, Phil ;
Petcherski, Andrei ;
Rogers, Anthony ;
Spooner, Will ;
Tuli, Mary Ann ;
Van Auken, Kimberly ;
Wang, Daniel ;
Durbin, Richard ;
Spieth, John ;
Stein, Lincoln D. ;
Sternberg, Paul W. .
NUCLEIC ACIDS RESEARCH, 2006, 34 :D475-D478
[79]   Invertebrate animal models of diseases as screening tools in drug discovery [J].
Segalat, Laurent .
ACS CHEMICAL BIOLOGY, 2007, 2 (04) :231-236
[80]   Drug discovery:: Here comes the worm [J].
Segalat, Laurent .
ACS CHEMICAL BIOLOGY, 2006, 1 (05) :277-278