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A Whole New Approach
CHORI Scientists Discover Reproductive Stage in Leishmania Parasites
In the cover publication of the September/October issue of The Journal of Eukaryotic Microbiology, CHORI scientists David M. Iovannisci, PhD, C. Paul Plested, PhD, and Gregory R Moe, PhD reveal first-time in vitro evidence of a newly identified sexual reproductive stage in the lifecycle of the Leishmania parasite responsible for afflicting 12 million people in 88 different countries across the globe. The study is a landmark discovery, which lays the foundation for the development of new genetic approaches to investigating this debilitating disease.

“What identifying this sexual reproductive stage means is that researchers now will be able to study the genetics of the parasite in the natural setting, as well as to more easily investigate genetic characteristics of interest for developing new avenues of treatment,” says Dr. Iovannisci.

“Researchers now will be able to study the genetics of the parasite in the natural setting , as well as to more easily investigate genetic characteristics of interest for developing new avenues of treatment.”

Leishmaniasis is transmitted by blood feeding insects like the sand fly, similar to the way malaria is transmitted by mosquitoes. There are three different levels of infection: a localized infection at the site of the insect bite, which creates an ulcerating sore that sometimes resolves and sometimes is chronic; a mucocutaneous infection in which the Leishmania have a preference for the mucus membranes, and a third type of infection in which the organism goes into the internal organs of the body.

"These latter two types of infections can be very serious. With mucocutaneous infections, the eyes, nose and mouth are targeted and the results can be very disfiguring, while when the internal organs are targeted, the infection can be deadly," says Dr. Iovannisci.

Unfortunately, current treatments have been limited by the complexity of the Leishmania parasite, and in particular, by the limited ability to develop genetic recombinantsin the laboratory.

“Leishmaniasis is such an enormous world wide health problem in particular because Leishmania can live both in mammalian host blood cells, as well as inside the gut of insect vectors,” explains Dr. Iovannisci.

"These are two very different environments that require Leishamania to have a variety of different lifecycle stages, making them very complex to both study and eradicate."
“These are two very different environments that require Leishamania to have a variety of different lifecycle stages, making them very complex to both study and eradicate.”
Until now. By combining their expertise in two different research areas, Drs. Iovannisci and Moe have successfully identified what they believe is a sexual reproductive stage in the Leishmania lifecycle that may open the door at last to the genetics of the organism and the key to its treatment or prevention.

"It turns out that the insect vector stage of Leishmania make what is called poly-alpha2,8 N-acetyl neuraminic acid or polysialic acid (PSA), a long polymer of carbohydrate," explains Dr. Moe, whose lab has been particularly interested for some time in PSA, and a derivative of PSA, called de-N-acetyl neuraminic acid-containing PSA (NeuPSA), because of its role in meningitis infections.


Read More about the Therapeutic Implications of Identifying this New Leishmania Stage

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Tuesday, May 17, 2011 8:19 AM

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