elegans is well characterized and is amenable to forward genetic analysis and molecular dissection. Thus, worm genes that are required for the bacterial infection to proceed can be mutated and studied. Mutations in these genes will confer resistance to M. nematophilum infection. For example, mutations in genes required for the proper expression of extracellular proteins on the cuticle of the worm, confer resistance to the bacteria. This suggests that the bacteria DESCRIPTION (provided by applicant): How does an animal respond to a bacterial infection? Caenorhabditis elegans is a free-living soil nematode that can be infected by the bacterium Microbacterium nematophilum. Unlike other bacterial pathogens of C. elegans, M nematophilum does not kill the worm, rather, the bacteria adheres to the tail of the worm causing constipation and a distinct deformed anal region phenotype. Therefore, this interaction is reminiscent of a chronic disease state rather than a general toxicity response. Although M nematophilum is in the poorly characterized coryneform family of bacteria, C. rely on these cuticle factors during pathogenesis. In addition, 11 other bacterial resistance-conferring mutations termed bus for bacterial unswollen were mapped in the Hodgkin laboratory. These genes remain to be characterized. Alternatively, worm genes used to defend against the bacterial pathogen can be mutated and studied. Mutations in these genes will confer hypersensitivity to M. nematophilum infection. Screens for these genes uncovered three mutations that fall into two classes, gmp (growth impaired by M nematophilum pathogen) and emp (excess deformation by M nematophilum pathogen). These genes also remain to be cloned and characterized. Thus characterization of mutations that alters the host response to this pathogen should not only uncover the molecular pathways required for a bacterial infection process but also the molecular pathways used by the host to fight infection. To fully understand how C. elegans responds to M nematophilum, the bacterial resistance and hypersensitive screens will be saturated to find all of the genes involved in this process. In addition the genes already isolated will be cloned and characterized.
