Nematode provides new animal model for emerging pathogen

Caenorhabditis elegans Microsporidia are single-celled parasites that are capable of causing infections in humans – primarily in people with compromised immune systems, such as those infected with HIV or who have undergone organ transplants. A new article documents a recently discovered species of microsporidian which infects Caenorhabditis elegans, the harmless worm used as a model system by developmental biologists. The work is a breakthrough for public health researchers who had been looking for a suitable laboratory model in which to study microsporidia. Microsporidia are classified as priority pathogens by the U.S. National Institutes of Health, since they have been found in water supplies and because no drugs are available for treating the most common infections they cause in humans. The new species infects C. elegans, a small roundworm that is very easy to study in the lab, and so provides a powerful system in which to study these mysterious microbes, learn how animals respond to infection and develop new drugs to fight infections of microsporidia.

The discovery is particularly exciting because it potentially offers a unique opportunity to identify new drugs for treating human microsporidian infections. The researchers named the new species of microsporidian Nematocida parisii, or “nematode killer from Paris”, because it was discovered in the intestines of roundworms found in Parisian compost pits. Since then, scientists have found closely related naturally-occurring pathogens in Portugal and India, leading them to conclude that they are widespread natural parasites of C. elegans, which has intestinal cells that look almost exactly like human intestinal cells, so researchers are able to tell what the parasites are doing to intestinal cells as they invading and exit the cells. Because the worms are completely transparent, they can take intact worms, put them on slides and see what’s happening. They have already seen some interesting changes in the structure of intestinal cells during different time periods of infection.

Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans. 2008 PLoS Biol 6(12): e309
For decades the soil nematode Caenorhabditis elegans has been an important model system for biology, but little is known about its natural ecology. Recently, C. elegans has become the focus of studies of innate immunity and several pathogens have been shown to cause lethal intestinal infections in C. elegans. However none of these pathogens has been shown to invade nematode intestinal cells, and no pathogen has been isolated from wild-caught C. elegans. Here we describe an intracellular pathogen isolated from wild-caught C. elegans that we show is a new species of microsporidia. Microsporidia comprise a large class of eukaryotic intracellular parasites that are medically and agriculturally important, but poorly understood. We show that microsporidian infection of the C. elegans intestine proceeds through distinct stages and is transmitted horizontally. Disruption of a conserved cytoskeletal structure in the intestine called the terminal web correlates with the release of microsporidian spores from infected cells, and appears to be part of a novel mechanism by which intracellular pathogens exit from infected cells. Unlike in bacterial intestinal infections, the p38 MAPK and insulin/insulin-like growth factor (IGF) signaling pathways do not appear to play substantial roles in resistance to microsporidian infection in C. elegans. We found microsporidia in multiple wildcaught isolates of Caenorhabditis nematodes from diverse geographic locations. These results indicate that microsporidia are common parasites of C. elegans in the wild. In addition, the interaction between C. elegans and its natural microsporidian parasites provides a system in which to dissect intracellular intestinal infection in vivo and insight into the diversity of pathogenic mechanisms used by intracellular microbes.

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