Why TB bacteria change their ESX1 virulence system
Identifying the drivers of ESX1 evolution in Mycobacterium tuberculosis
This project looks at whether natural changes in a TB bacterial system called ESX1 change how well antibiotics work for people with tuberculosis.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Harvard University D/b/a Harvard School of Public Health NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11230225 on NIH RePORTER |
What this research studies
Researchers will use genetic and laboratory experiments to recreate common ESX1 variants found in human TB strains and measure how those changes affect ESX1 function in the lab. They will then test these altered bacteria in mouse and macrophage models to see how the bacteria interact with immune cells and respond to standard antibiotics. The team combines population genomics from patient-derived TB samples with laboratory studies to link specific bacterial changes to treatment outcomes. This early-stage work aims to build foundational evidence for a concept they call 'virulence-associated drug resistance.'
Who could benefit from this research
Good fit: People with active pulmonary TB—especially those who can provide bacterial samples or who have experienced treatment failure—would be most relevant to this research.
Not a fit: People without TB, those with non-tuberculous mycobacterial infections, or patients already cured are unlikely to receive direct benefit from this lab-focused project.
Why it matters
Potential benefit: If correct, this work could explain some unexplained TB treatment failures and lead to tests or therapies that improve cure rates.
How similar studies have performed: Previous genomic and lab studies have shown that ESX1 affects TB virulence and that bacterial genetics can influence treatment, but directly linking natural ESX1 variants to antibiotic response is a new and early-line idea.
Where this research is happening
Boston, United States
- Harvard University D/b/a Harvard School of Public Health — Boston, United States (Active)
Researchers
- Principal investigator: Fortune, Sarah — Harvard University D/b/a Harvard School of Public Health
- Study coordinator: Fortune, Sarah
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 below.