The eggs of Trichuris muris, a whipworm parasite of mice, cannot hatch without help from gut bacteria, according to Richard K. Grencis, Ian S. Roberts, and their colleagues at the University of Manchester in the United Kingdom.  The bacteria cluster at opercula, portals for emerging whipworm larvae, and trigger hatching by attaching their fimbriae to pole receptors. This relationship strongly suggests that the whipworms, bacteria, and rodents have a long evolutionary history together and worms, like bacteria, play an important role in modulating mammalian immune systems, the researchers say. Details appear in the 11 June 2010 Science (328: 1391-1394).

Whipworms are parasitic nematodes infecting a wide range of mammalian species, including about 1 billion humans worldwide. After ingested eggs hatch, the whipworm larvae burrow into the host intestinal wall, lodging in the crypts of Lieberku¨ hn. The larval worms eventually migrate downwards, take up residence in the cecum and colon, mate, and release eggs into the environment. A life spent in the nether regions of the intestines, where worms readily release their eggs via host feces, enables them to disperse widely. Notably, adult worms live for about one year, and each female produces 5,000 to 20,000 eggs per day.

The researchers analyzed bacterially driven hatching mechanisms at first by using explants of mouse cecum that were colonized with enteric bacteria. These experiments indicated that hatching depends on direct contact between microbes and eggs at 37°C. The researchers next incubated mouse whipworm eggs with cultured Escherichia coli cells, which induced levels of hatching similar to those induced by mixtures of enteric microbes.

Moreover, when E. coli cell components were filtered out, the eggs lay dormant, indicating that a structural component of the bacterium, not a secreted molecule, is necessary for hatching. Boiling the E. coli prevented hatching, whereas treating the bacteria with the bacteriostatic antibiotic gentamicin had no effect on hatching. "It didn't appear to matter if the bacteria were viable or not, just that they were intact," says project leader Kelly Hayes.

"These findings, taken together, confirmed our initial hunch that bacteria assembling at the ends of Trichuris eggs were physically contacting the eggs rather than communicating via a chemical messenger and that an intact bacterial surface is a critical component of the hatching process," Roberts says.

Further analysis confirms that other microorganisms-one yeast and five different bacterial strains-are also efficient Trichuris hatch inducers. Type 1 fimbriae are key but not absolutely required mediators of this process. Neither Pseudomonas aeruginosa nor Staphylococcus aureus, for example, has these particular fimbriae, yet they induce whipworm larvae to hatch, suggesting to Grencis that other bacterial components are also effective hatch triggers.

While the researchers would not encourage people to infect themselves with parasitic worms, they do contend that "having a low number of worms -not enough to do any harm-may be an effective way to develop a robust immune response." T. muris and other macrofauna might also modulate gut inflammation and autoimmune reactions. "The gut and its inhabitants are a complex ecosystem, and if the worms are missing, the immune system may not give the right response," Roberts says.

"Eventually physicians may be colonizing patients at risk for some immune- related disorder with helminths, and the information in this paper could help develop the necessary technology to do this efficiently," says William Parker from Duke University in Durham, N.C. "Self-administration of whipworms, which is going on today, is unwise for a number of reasons," he adds, citing the accidental ingestion of dangerous pathogens and conditions such as immunosuppression or anemia that would make such "therapy" dangerous. "These problems will be easily avoided when medical specialists take charge and begin putting back some of the larger gut creatures that our overly hygienic Western environment has removed."

Marcia Stone

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