VOLUME 24 NUMBER 9 SEPTEMBER 2006 NATURE BIOTECHNOLOGY a key DNA-binding protein that allows transcription of virulence factors, as the target of virstatin, a V. cholera virulence inhibitor3. Although identifying mechanisms of action that target host responses will be challenging, a recent high-throughput screen of C. elegans to identify growth-altering compounds9 seems noteworthy. In this work, a library of 180,000 randomly mutated C. elegans strains was used to identify a calcium channel subunit as the target of nemadipine-A. Although the in vivo virulence screen designed by Ausubel and colleagues shows great potential, it may require further optimization to become compatible with industrial-scale high-throughput screening. A promising development in this regard is the use of automated inoculation and imaging of nematodes by Kwok et al.9. The easily scored morphological differences between live and dead worms observed in screens for nontraditional antimicrobials should be amenable to such automation. Finally, the suitability of C. elegans as a model infection system deserves reconsideration. As pointed out by the authors, C. elegans can feed on several human pathogens, including the troublesome Gram negative pathogen Pseudomonas aeruginosa. However, although this model is responsive to E. faecalis, it is not susceptible to infection by other human pathogens, such as Enterococcus faecium.