How Brucella enzymes weaken immune defenses
Official title: Defining the role of the Brucella TIR-NAD hydrolase activity in immunosuppression and pathogenesis
Funded at University of Wisconsin-Madison · NIH-11324202 · Data updated 2026-11-12
This research looks at whether enzymes made by Brucella bacteria break down a key molecule in immune cells and help the bacteria cause infections in people.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Wisconsin-Madison NIH-funded |
| Lab location | 1 site (Madison, United States) |
| Project start | April 24, 2025 |
| Project end | March 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $194,375 |
| NIH project number | 5R21AI190247-02 |
| Project ID | NIH-11324202 on NIH RePORTER |
Who could benefit from this research
✓Could help
People who have or are at high risk for brucellosis (Brucella infection) would be the most likely candidates to benefit from future therapies based on this work.
✕Less likely to help
Patients with infections unrelated to Brucella or chronic conditions not driven by this bacterial mechanism are unlikely to benefit directly from these findings.
What this research studies
Researchers will study bacterial TIR-domain enzymes that cut nicotinamide adenine dinucleotide (NAD+) in immune cells to see how that changes immune signaling. In lab tests they will infect primary human-relevant immune cells (macrophages and dendritic cells) and measure NF-κB activation and inflammatory cytokine responses while tracking where the bacterial effectors go inside cells. The team will also use genetically altered Brucella strains with disabled enzyme activity and test their effects in mice to see whether the enzyme changes how well the bacteria cause disease. Results will combine cell-based activity, localization, and animal outcome data to link the enzyme activity to immune suppression and virulence.
Why it matters
Potential benefit: If successful, this work could reveal a new bacterial mechanism to block immunity and point to targets for drugs or vaccines against brucellosis.
How similar studies have gone: Laboratory work recently showed that some bacterial TIR enzymes can break down NAD+, but directly linking that activity to Brucella virulence in infected animals is a new direction.
Where this research is happening
-
University of Wisconsin-Madison
Madison, United States Active
Researchers
- Principal investigator: Salcedo, Suzana P — University of Wisconsin-Madison
- Study coordinator: Salcedo, Suzana P
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About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.