# Role of African Trypanosome Extracellular Vesicles in Infection and Pathogenesis

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $375,000

## Abstract

Intercellular communication between parasites and with host cells provides mechanisms for parasite
development, immune evasion and disease pathology. Bloodstream African trypanosomes produce
membranous nanotubes (NTs) that originate from the flagellar membrane and disassociate into free
extracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute to
virulence in the mammalian host including calflagin, adenylate cyclase (GRESAG4),
glycosylphosphatidylinositol phospholipase C (GPI-PLC), calreticulin and metacaspase 4. In addition,
the human sleeping sickness parasite Trypanosoma brucei rhodesiense produces EVs that contain
the serum resistance associated protein (SRA) a virulence factor necessary for human infectivity. We
have shown that T. b. rhodesiense EVs transfer SRA to non-human infectious trypanosomes allowing
evasion of human innate immunity. Morphological and biophysical studies have shown that
trypanosome EVs can also fuse with phosphatidylcholine liposomes, the trypanosome flagellar pocket
and mammalian erythrocytes. Trypanosome EV fusion with erythrocytes alters the physical properties
of erythrocytes increasing membrane rigidity resulting in rapid erythrocyte clearance and anemia. The
proposed studies will extend these initial findings and address several fundamental questions about
the function of membrane NTs and EVs. 1) Are EVs produced during trypanosome infection and if so
what is the rate of production and does EV cargo change during the course of infection? 2) Do EVs
deliver quorum-sensing molecules that trigger differentiation of BF trypanosomes? 3) Does the NT/EV
pathway provide an efflux mechanism to rid human sleeping sickness parasites of trypanosome lytic
factors (TLF)? 4) Do EVs deliver trypanosome effector molecules that modulate production of the
cytokine, tumor necrosis factor-α, in myeloid cells? 5) Does the fusion of trypanosome EVs with host
erythrocytes result in erythrophagocytosis and anemia? 6) What trypanosome proteins are necessary
for EVs fusion to membranes? Together the proposed studies will result in a better understanding of
the role of trypanosome EVs in cell-cell communication and pathogenesis associated by African
trypanosomiasis. We anticipate these studies will lead to the development of new diagnostic tools and
offer novel strategies to combat anemia in human sleeping sickness and Nagana.

## Key facts

- **NIH application ID:** 9851329
- **Project number:** 5R01AI125487-04
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** STEPHEN L HAJDUK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,000
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851329

## Citation

> US National Institutes of Health, RePORTER application 9851329, Role of African Trypanosome Extracellular Vesicles in Infection and Pathogenesis (5R01AI125487-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851329. Licensed CC0.

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