Recognition of social behavior and cell-cell signaling as a ubiquitous property of bacteria revolutionized our understanding of microbiology and microbial pathogenesis. Parasitic protozoa generally are not considered in this context. Recent work however, demonstrates that the paradigm of microbes as social organisms can and should be brought to bear on questions about parasite biology, transmission and pathogenesis. African trypanosomes, e.g. Trypanosoma brucei, and related trypanosomatid parasites are responsible for substantial human suffering worldwide. T. brucei is transmitted between human hosts by tsetse flies. The parasites live in communities in which they can communicate with one another and engage in group behaviors that are not evident in individual cells, this behavior is termed ?Social Motility? (SoMo) and shows analogies to social behavior in bacteria. Studies of SoMo have generated insight into parasite development, transmission, signaling and chemotaxis. In the current proposal we will use recently developed SoMo mutants and new tools for imaging parasites in mixed populations to determine the role of social behavior and cAMP for infection of tsetse flies, define gene expression programs that govern social behavior and tsetse fly infection, and dissect mechanisms of parasite chemotaxis. We expect our studies will provide new perspectives and approaches for understanding parasite biology, which in turn are necessary to develop novel strategies for management and therapeutic intervention in parasitic disease.

Public Health Relevance

Trypanosomatids are protozoan parasites that cause substantial human suffering worldwide. The paradigm of microbial social behavior revolutionized our understanding of bacterial pathogenesis and can now be applied to protozoan parasites. In the current project, we will apply these concepts to trypanosomatids to give insight into parasite biology, transmission and host-parasite interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI133166-02
Application #
9698280
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Mcgugan, Glen C
Project Start
2018-05-15
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2021-04-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095