With certain forms of dysentery, an amoeba attacks the intestine by biting off and eating pieces of the cells. Researchers used to think that the amoeba secretes toxic molecules to kill the cells before eating them, but grisly new work shows that the cells were eaten alive.
Amoebiasis is a potentially fatal and bloody diarrheal infection that leads to amoebic dysentery, killing 100,000 people a year. Now that researchers have uncovered the processes that drive this ingestion of living intestinal cells, they hope it leads to treatments for people living in places with poor sanitary conditions.
The single-celled parasite responsible is called Entamoeba histolytica, and its infection results in lots of tissue destruction, causing intestinal ulcers and abscesses. Even its name -- Greek histos and lysis for "tissue" and "to separate" -- refers to its ability to destroy host tissue. Researchers have previously proposed that the amoebae kill the cells before ingesting them. Unfortunately, as it turns out, the reverse happens: ingestion is required for killing the cells.
A team led by William Petri from the University of Virginia, Charlottesville, made the macabre discovery by using live microscopy to capture amoebae on camera. Their video revealed amoebae nibbling away at live human cells, eating them piece by piece. "They are impressively ravenous," lead author Katherine Ralston of U.Va. tells New Scientist.
After it glues itself to a cell using proteins called lectins, E. histolytica takes many small, distinct bites of living cells. It begins tearing off and ingesting bits within a minute of contact, and the cell dies about 10 minutes later. Cell death probably stems from accumulation of damage, with elevations of intracellular calcium. Once the cells are dead, the amoebae detach, stop ingestion, and effectively spit out the corpses.
Here, E. histolytica (pre-labeled blue) ingesting bites of mouse intestine cells (tagged with fluorescent green protein) captured using live two-photon microscopy.
Amoebae are known to feed by phagocytosis: with one cell completely engulfing another. (Think back to all those comics.) That’s probably why researchers assumed the amoebae ingested the intestine cells whole. In fact, when offered dead cells, amoebae simply swallowed them -- no small bites. Instead, this nibbling of live cells is similar to a process called trogocytosis (from Greek trogo for “to nibble”). This is known to happen with immune cells, but never during host-parasite interactions like this one. Amoebic trogocytosis is also different because it results in untimely death and seems to have nothing to do with clearing out dead cells for maintenance or nutrition.
If E. histolytica is constantly grazing throughout the intestines, it may be able to lurk inside a host for years without causing an inflammation. Or maybe the amoeba sneaks past immune cells by flooding the gut with cellular corpses. “Maybe by leaving the dead cells for the macrophages to eat, it leaves a decoy for the immune system,” Petri tells The Scientist. These speculations could explain why infected people sometimes show no symptoms at all.
The team tried using a drug that interferes with the amoeba’s ability to reshape itself, and they also genetically modified amoebae that couldn’t produce lectins and related proteins. The results were amoebae that devoured less, demonstrating that the inhibition of certain molecular processes in E. histolytica can prevent cell death.
The work was published in Nature this week.
Images: Katy Ralston (top), Katy Ralston and David Zemo (middle)