Caenorhabditis elegans Meets Microsporidia: The Nematode Killers from Paris

Primer I ntracellular invasion is a great strategy for a microbial pathogen. By colonizing the cytoplasm or an intracellular compartment, the pathogen is shielded from many host defenses and gains privileged access to cellular nutrients. Intracellular pathogens are familiar in mammalian systems, in the form of bacteria such as Mycobacterium [1] and Listeria [2], and eukaryotic parasites such as Leishmania [3] and Trypanosoma cruzi [4]. The mechanisms whereby they get into cells and survive and multiply within them are central to their pathogenicity. Also, such pathogens often subvert host cellular machinery in interesting and informative ways. For example, the ability of Listeria cells to make " comet tails " of actin in order to propel themselves around cells has provided useful tools for investigating actin-based movement [5]. The invasion strategy is evidently ancient, and occurs even within bacteria themselves, in the form of bdellovibrios, which are bacteria able to live under the cell wall of other bacteria [6]. And the cytoplasm of all eukaryotic cells carries the inheritance of a primordial bacterial colonization, in the form of mitochondria and their derivatives. Many pathogens of invertebrates are also able to invade cells; one important instance is the penetration of insect gut cells by the malaria parasite during the mosquito phase of its lifecycle [7]. For nematodes, which constitute a vast and much studied invertebrate phylum, however, there have been few previous reports of pathogens capable of penetrating and multiplying within host cells. Nematodes are protected on the outside with an extremely tough and impermeable cuticle, which provides an excellent barrier against external attack. A few specialized parasites are able to drill through this armor plate and proliferate within the worm, such as the fungus Drechmeria coniospora [8] and the bacterium Pasteuria penetrans [9], but most diseases of nematodes involve attack from inside, via colonization of the alimentary tract, which is necessarily a more vulnerable tissue. Many free-living nematodes live by feeding on bacteria, so in a natural environment their guts are constantly exposed to a wide spectrum of potentially pathogenic microbes. Some of these can cause disease and ultimately death of infected worms, but the usual pattern of disease involves proliferation within the gut lumen, without any penetration of host cells. A new pathogen, reported by Troemel et al. in this issue of PLoS Biology [10], significantly expands the roster of nematode diseases with the discovery of a microsporidian fungus able …