host-pathogen interactions

host-pathogen interaction

Caenorhabditis elegans as a model to study host-pathogen interactions

Host-Pathogen interactions are antagonistic relationships in which the survival of each side depends on its ability to defeat the other. As a result of these interactions, host organisms have developed surveillance and defence systems within their bodies to detect and eliminate invading microbes. Interestingly, some of the key features of hosts' defence mechanisms as well as the strategies employed by pathogenic microbes appear to have ancient origins and are seemingly conserved through phylogeny. Therefore, it is reasonable to believe that useful insights into the human-pathogen interactions can be gained from the use of invertebrates as models in cases that the pathogen can infect both humans and the model.

One of the simplest invertebrate models is the nematode worm Caenorhabditis elegans. This soil-dwelling worm, which has the length of only 1 mm, has been the subject of intense study for more than 20 years. C. elegans has several characteristics (e.g. simple growth conditions and rapid generation-time with consistent cell lineage) that qualify it as an acceptable model to study host-pathogen interactions. Indeed, the availability of C. elegans as a genetically tractable model have helped researches identify a myriad of genes involved in the organism's defence mechanisms as wells as virulence factors involved in pathogenisity of microbes.

C.elegans has been used as a host model for several opportunistic pathogens, among which Pseudomonas aeruginosa, Salmonella typhimurium and, Serratia marcescens are prominent examples. Studying mutants of these pathogens and their virulence in C.elegans can help us elucidate the importance of specific genes in pathogenicity of these bacteria and help us build better therapeutic strategies for humans. Moreover, characterization of C. elegans mutants and their reduced or enhanced resistance to pathogens can shed light on host defence strategies and the genes involved in those strategies. The completion of the worm genome project can become extremely useful for depicting the gene expression profiling in such defence mechanisms. For instance, having the whole genome sequence will enable us to use microarrays in order to determine the specific C. elegans genes that are expressed in its defence against pathogens. This capacity to take a two-sided genetic approach (i.e. characterization of the pathogen's virulence factors and the host's defence mechanisms) holds great promise for the future studies on interactions between various pathogens and their human host.

Examples of pathogens that infect C. elegans:

1. Pseudomonas aeruginosa: an opportunistic gram-negative bacterial pathogen that is a major cause of bacteremia in humans.

2. Salmonella typhimurium: another gram negative bacterium that can be a cause of diarrhoea and salmonellosis in humans

3. Serratia marcescens: another gram negative bacterium can cause meningitis, endocarditis and pyelonephritis in humans.

Useful Techniques in Studying Host-Pathogen interactions

1. Liquid culture of worms with Fermentor: Mimi H. Zhou e.t al.

2. in situ hybridization for the detection of RNA in C. elegans embryos: Geraldine Seydoux and Andrew Fire

references

Avery, L. January 2002. Caenorhabditis elegans WWW Server, http://elegans.swmed.edu/, accessed March 2002.

Finlay, B. B., (1999), Bacterial disease in diverse hosts. Cell 96: 47-56.

Kurz, C.L., and Ewbank, J. J. 2000. Caenorhabditis elegans for the study of host-pathogen interaction, Trends in Microbiology. Vol 8 (3):142-44.

Abbalay, A., Yorgey, P., and Ausubel, F.M. 2000. Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans, Current Biology 10:1539-1542.

Labrousse, A., Chauvet, S., Couillault, C., Kurz, C.L., and Ewbank, J.J. 2000. Current Biology 10:1543-1545. Tan, M, Mahajan-Miklos, S, and Ausubel, F.M. 1998. Killing of Caenorhabditis elegans by Peudomonas aeruginosa used to model mammalian bacterial pathogenesis, Proc. Natl. Acad. Sci. USA 96: 715-720.