Future Directions Testing Additional Model Hosts

We were surprised that genes identified as PA14-virulence determinants are not necessarily correlated with the virulence of other strains in which they are found, because this observation suggests that the action of some virulence determinants may depend on the total genomic content. This view contrasts with canonical pathogenicity islands that contain a set of genes acting as an autonomous set, the presence of which directly contributes to overall strain virulence. Since most studies of pathogenicity islands have been carried out in more traditional experimental systems, it is possible that our unexpected observations are a result of using a model host such as C. elegans. Traditional infection systems using mice or other mammals involve a single dose of bacteria, often administered at a low titer and requiring the initial population of pathogens to proliferate and avoid detection by the host's immune response long enough to reach a pathogenic or lethal dose. In contrast, the C. elegans infection system constantly exposes the host to a maximal does of pathogen. The former approach has conceptual similarity to an acute infection in humans, whereas the latter has aspects that more closely approximate a chronic infection.

An advantage of the model host approach to studying infectious disease is that multiple hosts can be used and compared, each with their respective strengths and weaknesses. One alternate host that we are currently examining is the greater wax moth caterpillar, G. mellonella. Wax moth caterpillars are commercially available, inexpensive, easy to use, and yield data rapidly, making them an ideal candidate for pilot experiments to extend our observations in C. elegans to other host organisms.

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