n the comfortable culture of the U.S., which we take for granted all too often, it can be difficult to remember the human plagues and diseases that have followed mankind throughout the millennia. It’s difficult to remember that we, ourselves, are the preferred breeding ground for a host of bugs, worms and parasites; not just idle or incidental carriers of these microscopic beasts, but their main course…dependent on our unique physiology in order to reproduce and survive.
Some of these diseases are famous, due to their pugnacious nature or severity of effect; diseases such as malaria, botulism, or River Blindness. Others are less well known, either due to their more limited environment or because their incidence in more developed countries is less common, such as the protozoan, Entamoeba histolytica. However, less common does not necessarily mean less destructive. Entamoeba is a group of anaerobic parasites that specifically target humans and primates. Typically passed from feces and water to another host in a cystic form, these protozoans mature in our digestive tracts and cause a disease called Amebiasis. Amebiasis is typically characterized by abdominal pain, amebic dysentery, bloody diarrhea, and fevers. The protozoans can also occasionally escape the colon and end up on other organs to cause liver, brain or lung abscesses. Current estimates are that nearly 50 million people, worldwide, suffer infection from E. histolytica, which result in around 100,000 deaths. However, only 10-20% of all infections become symptomatic, so the number of infections may actually be much higher. The rate of infection of E. histolytica in tropical countries in Central or South America, Africa and Asia is actually nearer to 50%! And when the numbers of E. histolytica are combined with similar, but non-symptomatic protozoans (such as E. dispar and E. moshkovskii), the total world count may be closer to 10% or 500 million infective cases.
The most likely place to start looking for better methods of disease prevention of Amebiasis are the surface protein interactions between the protozoan and our intestinal walls which cause adherence and activation of the protozoan to its trophozoite stage. Cataloguing and defining these surface proteins is about as easy as identifying all of the various countries on Earth from a telescope on Mars. To date, only a smattering of about 20 of these surface proteins had been identified. Iris Bruchhaus and her group from the Nocht Institute for Tropical Disease wanted to blow that number away and settle once and for all what proteins need to be studied.
Bruchhaus’ group used a non-permeable biotinylation process to bind with all of the surface proteins on the HM1:IMSS strain of E. histolytica. Those biotin conjugated proteins were then easily isolated using a streptavidin agarose resin system (which you can also conveniently find here), and analyzed in NanoLC-MS/MS in order to identify the proteins. They found close to 700 proteins! Oddly though, nearly 50% of the proteins found they found did not show any specific membrane association. Bruchhaus’ group was able to further detail many of these isolated oddball proteins, showing that roughly 85% of them did have some cell surface interaction, even if not in the traditional sense. But this actually implies that the plasma membranes (and their surface associations) of these protozoans are not static and easily defined at all, but are a very dynamic, complex and interconnected weaving of molecules in constant exchange on and across the membrane.
That doesn’t necessarily make this type of work any easier. But with a large number these proteins identified, work can at least begin on some of the most important proteins, further characterizing the association with their human host cells. Who knows, maybe it’s actually one of these oddball proteins that only sometimes associates with the plasma membrane that account for the low percentage of the protozoan becoming symptomatic. Time will tell…
Biller, L., Matthiesen, J., Kühne, V., Lotter, H., Handal, G., Nozaki, T., Saito-Nakano, Y., Schumann, M., Roeder, T., Roeder, E., Krause, E., & Bruchhaus, I. (2014). The Cell Surface Proteome of Entamoeba histolytica. Molecular & Cellular Proteomics, 13(1), 132-144.
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