# Leishmania amazonensis sabotages host SUMOylation: a novel virulence mechanism for macrophage invasion

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $209,375

## Abstract

This proposal is focused in the study a novel Leishmania virulence strategy involved
in the successful infection of mammalian macrophages — inhibition of protein
SUMOylation. This virulence mechanism was discovered has a result of a cell-based
genome-wide RNAi screen using Drosophila cells. The knockdown of several
SUMOylation factors affected infection by amastigotes forms of Leishmania
amazonensis, and further studies in mammalian macrophages revealed that L.
amazonensis infection inhibited host cell SUMOylation and depletion of SUMO factor
enhanced parasite replication.
 SUMOylation is a post-translational modification in which a member of Small
Ubiquitin-like MOdifier protein (SUMO) is conjugated to target proteins. SUMOylation
regulates numerous protein functions or activities, and over six thousand different
SUMOylated proteins have been cataloged in HeLa and U2OS cell lines. Given its
ubiquitous role in cells, we hypothesize that SUMOylation inhibition is one important
virulence mechanisms of L. amazonensis.
 Supporting this idea, infection of SUMO depleted macrophages produced larger
parasitophorous vacuoles (the replicative niche) and higher parasite proliferation. The
participation of SUMOylation in parasitophorous biogenesis and in parasite replication
will be studied in more detail.
 In a broader context, we will also determine how parasites affect SUMOylation and
what is the relevance of this virulence strategy in mouse infection. Briefly, we will
determine what components of the host SUMO machinery are targeted by parasites and
identify parasitic virulence factors. The relevance of SUMOylation inhibition in
leishmaniasis will be evaluated in infections of mice deficient in SUMOylation factors
and in studies correlating virulence of different leishmania strains and SUMOylation
inhibition capacity.

## Key facts

- **NIH application ID:** 10170253
- **Project number:** 5R21AI154208-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Kendi Okuda
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2020-05-22 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170253

## Citation

> US National Institutes of Health, RePORTER application 10170253, Leishmania amazonensis sabotages host SUMOylation: a novel virulence mechanism for macrophage invasion (5R21AI154208-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10170253. Licensed CC0.

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