Why has C. elegans been extensively used to investigating host-microbial associations? One answer lies in the powerful resources available for forward and reverse genetic analysis in this organism. Mutagenesis to generate C. elegans strains resistant or hypersensitive to pathogens can be easily accomplished (Darby et al. 2007; Gravato-Nobre and Hodgkin 2005; Marroquin et al. 2000; Pradel and Ewbank 2004; Tan and Ausubel 2000; Yook and Hodgkin 2007). C. elegans is a convenient, simple, ethically acceptable, and inexpensive model host. With its 3-day generation time at 20oC, and 1 mm adult length, the worm can easily be grown in microtiter plates and is small enough for automated liquid sorting. This feature makes it amenable for whole-organism in vivo screening of libraries of antimicrobial compounds (Breger et al. 2007; Moy et al. 2006). The small cell number (959 somatic nuclei) and the transparency of its body also make C. elegans attractive for studying microbial infections. By using transgenic lines bearing fluorescent reporters, C. elegans is well suited for in vivo imaging of genes specifically modulated upon infection. Moreover, appropriately tagged pathogens can easily be followed in vivo and used to dissect biological aspects of their host pathogenicity (Sifri et al. 2003; Tenor and Aballay 2008).
In laboratory culture, C. elegans is grown on bacterial lawns. Such property is advantageous for two main reasons: firstly, because it provides a convenient route of microbial infection analysis and, secondly, bacterial feeding can be used for the application of RNA interference (RNAi)-based gene silencing. Genome-scale screens using feeding RNAi are now commonplace (Boutros and Ahringer 2008). RNAi has been efficiently used to inhibit gene function and to identify new resistance and susceptibility genes that cannot easily be targeted by using mutagenesis-based approaches. Homologues of genes implicated in defense in other organisms can rapidly be tested in C. elegans by this means (Alper et al. 2007, 2008). Using a combination of genetic strategies, several groups have now been able to establish the roles of transducers that mediate interactions between C. elegans and pathogenic microorganisms. One theme emerging from such approaches is that the innate immune mechanisms of C. elegans and that of the flies, mammals and plants, share striking similarities (Alper et al. 2007; Kurz and Ewbank 2003; O'Rourke et al. 2006; Tan and Ausubel 2000).
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