MBL, WOODS HOLE, MA -- For years biomedical researchers have known that high density lipoproteins, commonly called HDLs or "good cholesterol," are responsible for protecting humans from certain parasites, but couldn't explain how. Now MBL scientists have discovered that human HDLs work this bug-repelling magic by serving as a platform for the assembly and delivery of two naturally occurring proteins that combine to create a super-toxic antimicrobial.
The research, published in the September 30 issue of the Journal of Biological Chemistry, focuses specifically on human innate immunity to Trypanosoma brucei brucei, the parasite that gives African cattle the deadly disease called Nagana, but which doesn't harm humans even though scientists believe they are exposed to it. The parasite is a close relative of Trypanosoma brucei gambienese and Trypanosoma brucei rhodesiense, the organisms that cause African sleeping sickness in humans.
The findings that two proteins work synergistically to kill the Nagana parasite in humans contradict a long-held hypothesis that a single protein was the key to HDL's parasite-fighting power. "The research may be helpful to veterinarians hoping to develop treatments to aid African cattle farmers, who lose three million cattle and around a billion US dollars annually to Nagana," says April Shiflett, a scientist in the MBL's Global Infectious Diseases Program and an author on the paper. Scientists also hope the research will provide key information to investigators seeking treatments for certain parasitic infections, such as malaria.
To identify the proteins--known as apolipoprotein L-1 (apo L-1) and haptoglobin-related protein (Hpr)--MBL scientists tested different amounts and combinations of the proteins on Trypanosoma brucei brucei specimens. To survive the parasite needs to digest the lipids in HDLs. Because HDL carries these proteins and enables them to combine, it is nature's perfect delivery system for the antimicrobial. And when test organisms digested the super-toxic protein mix, the single-celled organisms literally dissolved.
Shiflett and her colleagues in the MBL's Global Infectious Diseases Program are focused on understanding the molecular workings of a variety of parasites, including those that cause human African sleeping sickness, Nagana, and malaria. Such research is crucial to finding creating better treatments, and possibly cures, for diseases that are ravaging the people and economies of places like Africa and other developing countries.
Funding for this study was provided by the National Institutes of Health. The complete paper can be found in the Journal of Biological Chemistry, Volume 280, Number 38.
The MBL is an internationally known, independent, nonprofit institution dedicated to improving the human condition through creative research and education in the biological, biomedical and environmental sciences. Founded in 1888, as the Marine Biological Laboratory, the MBL is the oldest private marine laboratory in the Western Hemisphere. The Global Infectious Diseases Program is a part of the MBL's Josephine Bay Paul Center for Comparative Molecular Biology and Evolution. The Center explores the evolution and interaction of genomes of diverse organisms that play significant roles in environmental biology and human health. This dynamic research program integrates the powerful tools of genome science, molecular phylogenetics, and molecular ecology to advance our understanding of how living organisms are related to each other, to provide the tools to quantify and assess biodiversity, and to identify genes and underlying mechanisms of biomedical importance. For more information, visit the MBL website at http://www.MBL.edu.
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