Gut-Wrenching

The surface of a gerbil small intestine is nearly obscured by invading giardia protozoa.

CDC/Dr. Stan Erlandsen

The protozoan giardia is the most common illness-causing parasite in humans, triggering bouts of diarrhea and stomach pain in 280 million people annually. Despite its scourge, the exact mechanisms of giardia’s disease causation have eluded scientists since the “Father of Microbiology,” Antonie van Leeuwenhoek, discovered the parasite in 1681. A new study suggests that the key to giardia’s effectiveness lies in its ability to secrete various proteins that help it feed and thrive.

Kevin Tyler, a senior lecturer at the University of East Anglia’s Norwich Medical School, and colleagues infected cell cultures with giardia to identify which proteins released by the parasite interact with a host’s intestinal cells. Two significant protein families emerged. One family, the cathepsin B cysteine proteases, is known to slice through the gut’s protective mucus and into cells. The second family includes proteins known as tenascins, which closely mimic human proteins that regulate the adhesion between cells.

The researchers observed that the two kinds of proteins seem to work in concert to damage cells in the gut lining, allowing giardia—as well as opportunistic bacteria in the area—to consume the tissues’ vital nutrients. “Where the cathepsins cleave cells apart, the tenascins can prevent them from sealing back together,” said Tyler. The smorgasbord of exposed nutrients likely permit other potential pathogens in the gut to proliferate, explaining why giardia infections can severely affect some individuals.

Besides these two seemingly major players in giardia’s disease mechanism, Tyler and his team found evidence of contributions by other proteins. One of them grabs onto any available oxygen, allowing giardia, an anaerobic organism that requires an oxygen-free environment, to thrive better. Another secreted protein thins out the gut’s protective mucus, again aiding giardia in reaching the gut’s cellular lining.

More research will be needed to bear out the activity of the various giardia proteins in whole, living organisms, and not just in cell cultures. All the proteins could be promising drug targets. Novel approaches to treating giardia will become increasingly vital in the years ahead, as about a fifth of infections are already resistant to mainline drugs. “New, more specific drugs are indeed much needed for this disease,” said Tyler. (GigaScience)

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