Long considered a freewheeling loner, the Trypanosoma brucei parasite responsible for African sleeping sickness has revealed a totally unexpected social side, opening a potential chink in the behavioral armor of this and other supposedly solitary human parasites, according to research presented at the American Society for Cell Biology's 50th Annual Meeting in Philadelphia.
"The concept of bacteria acting as groups of cells communicating and cooperating with one another has had a major impact on our understanding of bacterial physiology and pathogenesis, but this paradigm has not been applied to parasitic protozoa," said Kent Hill, Ph.D., of University of California, Los Angeles, who presented the findings. "Social motility offers many potential advantages, such as facilitating colonization and navigation through host tissues."
The unexpected discovery that at the right time and on the right surface, T. brucei are extremely social reveals "a level of complexity and cooperatively to trypanosome behavior that was not previously recognized," said Hill.
It also suggests a whole repertoire of behavior for other "loner" parasites that are responsible for malaria and epidemic diarrhea.
These supposedly solitary protozoa were better known for their propeller-like flagella and for cycling between tsetse fly and human hosts. But seeded onto a semisolid surface, T. brucei during their tsetse fly stage collect into large multi-cellular communities whose members sense their environment, exchange messages, and coordinate their movements in response to external signals.
T. brucei's flagellum provided the clue about the parasite's social behavior, said Hill. While examining the proteins exposed on the outside of the trypanosome flagellum, he and his colleagues identified a family of surface-exposed receptors and downstream signaling cascades involved in cyclic adenosine monophosphate (cAMP) intracellular signal transduction.
Using genetics to block gene expression and drugs to block protein activity, the researchers found that their flagella possessed sensing and signaling systems that equipped trypanosomes for social behavior.
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Kent Hill, Ph.D.
University of California, Los Angeles
Hill will present, " Signaling pathways in the flagellum of Trypanosoma brucei are required for responding to external signals," Monday, Dec.13, 2010, 8:35-8:55 a.m., mini-symposium: Host-Pathogen Interactions, Room 113, Abstract 920.
Kent L. Hill1,2, Michael Oberholzer1, Miguel A. Lopez1 , Z. Pius Kabututu1 and James Wohlschlegel3
1-Department of Microbiology, Immunology and Molecular Genetics,
2-Molecular Biology Institute, and
3-Department of Biological Chemistry, UCLA, Los Angeles, CA, USA.
G. Zheng, S.D. Redick, S. Akbarian, Y. Guo, S. Doxsey
U Mass Medical School, Worcester, MA;
University of Pittsburgh School of Medicine, Pittsburgh, PA;
Q. Yu, R. Samtani, C. Lo
National Heart, Lung and Blood Institute, NIH, Bethesda, MD
Texas Scottish Rite Hospital for Children, Dallas, TX
Nemours/Alfred I. Dupont Hospital for Children, Wilmington, DE
Medical Research Council Human Genetics Unit, Edinburgh, UK
The Burroughs Wellcome Fund, NIH's National Institute of Allergy and Infectious Disease, and the Swiss National Science Foundation.