Abstract
For almost four decades, the nematode Caenorhabditis elegans has been of great value in many fields of biological research. It is now used extensively in studies of microbial pathogenesis and innate immunity. The worm lacks an adaptive immune system and relies solely on its innate immune defences to cope with pathogen attack. Infectious microbes, many of which are of clinical interest, trigger specific mechanisms of innate immunity, and provoke the expression of antifungal or antibacterial polypeptides. In this review, we highlight some of these families of antimicrobial peptides (AMPs) and proteins that are candidates for the development of novel antibiotics. In addition, we describe how systems of C. elegans infection provide an increasing number of possibilities for large-scale in vivo screens for the discovery of new antimicrobial drugs. These systems open promising perspectives for innovative human therapies.
Highlights
C. elegans as a model organismThe nematode Caenorhabditis elegans is a genetically tractable multicellular organism that has been the subject of intense study for more than four decades
It has been successfully used as a model system to address fundamental questions in multiple fields of biology, including development, neurobiology and aging. This tiny nematode worm has been applied to the study of microbial pathogenesis and host innate immunity, and used for drug discovery and development
Transgenic C. elegans strains can be readily created via microinjection of DNA, and its transparency renders the use of fluorescent reporter genes in vivo straightforward, as well as allowing direct real-time monitoring of infectious processes (Aballay et al, 2000; Labrousse et al, 2000)
Summary
The nematode Caenorhabditis elegans is a genetically tractable multicellular organism that has been the subject of intense study for more than four decades. Infection by the Gram-positive bacterium Microbacterium nematophilum causes a protective swelling response (Hodgkin et al, 2000; Nicholas and Hodgkin, 2004), whereas the fungal pathogen Drechmeria coniospora triggers an epidermal immune response characterized by the expression of antimicrobial genes encoding neuropeptidelike peptides (NLPs) and a family of closely related peptides named caenacins (CNCs) (Couillault et al, 2004; Pujol et al, 2008; Zugasti and Ewbank, 2009). In addition to enabling the identification of microcidal or microstatic molecules, the use of C. elegans allows detection of molecules that enhance immune defences in vivo Precisely this sort of drug candidate has been found in compound library screens that assay the effect of drugs on C. elegans survival following infection. An important improvement involved the application of a fluorescent dye that allowed the researchers to discriminate between live
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