Vital Parasite Protein That Enables Host Cell Invasion Identified

A protein has been identified that appears to play a key role in the process by which parasites such as those causing malaria and toxoplasmosis penetrate the cell membranes of their mammalian hosts.

Plasmodium falciparum, which causes malaria, and Toxoplasma gondii, which causes toxoplasmosis are members of the large group of parasites known as Apicomplexa. All members of this phylum have an infectious stage - the sporozoite - which possess three distinct structures in an apical complex. The apical complex consists of a set of spirally arranged microtubules (the conoid), a secretory body (the rhoptry), and one or more polar rings. Additional slender electron dense secretory bodies (micronemes) surrounded by one or two polar rings may also be present. It is this structure that gives the phylum its name.

Investigators at Boston College (MA, USA) used advanced gene mapping techniques to study mutant forms of T. gondii and P. falciparum that were unsuccessful in invading host cells. They reported in the January 13, 2012, edition of the journal Science that a single point mutation in the DOC2.1 protein was associated with a microneme secretion defect that prevented fusion of the parasite membrane with that of the host cell.

Micronemes are cellular organs, or organelles, possessed by Apicomplexa protozoans that are restricted to the apical third of the protozoan body. They are surrounded by a typical unit membrane. On electron microscopy, they have an electron-dense matrix due to the high protein content. They are specialized secretory organelles important for gliding motility and host cell invasion.

These organelles secrete several proteins such as P. falciparum apical membrane antigen-1 (PfAMA1), and erythrocyte family antigen (EBA) proteins. These proteins specialize in binding to erythrocyte surface receptors and facilitating erythrocyte entry. Only by this initial chemical exchange can the parasite enter into the erythrocyte via actin-myosin motor complex. It has been suggested that this organelle works cooperatively with its counterpart organelle, the rhoptry, which also is a secretory organelle.

“The mechanism of microneme secretion, which is required for host cell invasion, is a valid drug target,” said senior author Dr. Marc-Jan Gubbels, professor of biology at Boston College. “Since neither microneme secretion nor invasion itself are currently targeted by any antimalaria drugs, a potentially new class of antimalaria reagents can be developed. The high incidence of drug resistance against malaria is a big problem, so new drugs are urgently needed.”

“The resequencing method will permit the study of eukaryotic pathogens by forward genetics, which has shown its power in studies of model organisms, such as yeast and fruit flies,” said Dr. Gubbels. "To date, many of these pathogens have limited experimental and genetic accessibility, but this roadblock can now be lifted.”

Related Links:
Boston College