Avishek Mitra
Oklahoma State University, OK·Microbiology & Immunology
Tuberculosis has overtaken HIV/AIDS as the deadliest infectious disease, causing 1.2 million deaths in 2024, and drug-resistant strains are spreading. The bacterium responsible, Mycobacterium tuberculosis (Mtb), cannot colonize a person without iron.
- Fields
Microbiology & Immunology
Biochemistry
- Topics
Mycobacterium tuberculosis
Mtb
multidrug-resistant tuberculosis
- Grants
- 1 known grant, through May 2029
What they work on
- Determine how Rv0125, a protein Mtb releases outside the cell, strips heme from host hemoproteins such as hemoglobin, and whether it is a shared core component of the bacterium's heme uptake routes.
- Characterize how the heme-binding outer-membrane PPE proteins PPE36 and PPE64, which the lab finds can form pores, bind heme and interact with each other and the inner-membrane Dpp transporter to deliver heme to the cytoplasm.
- Define the albumin-dependent heme pathway, testing the idea that Mtb uses albumin-bound heme where blood is present, such as damaged lung tissue or the bloodstream.
- Measure how much heme iron acquisition contributes to Mtb replication inside alveolar macrophages, the lung cells the bacterium infects, by comparing heme-utilization mutants in infection models.
More about the research
Most human iron is not free: more than three quarters sits inside heme, the iron-containing molecule at the center of hemoglobin, the protein that carries oxygen in red blood cells. Mtb lives and divides inside macrophages, the same immune cells that break down worn-out red blood cells to recycle hemoglobin, so heme is probably a major iron supply for the bacterium during infection. The human body appears to fight back: the dead, necrotic cores of granulomas (the walled-off lesions formed around Mtb in patients' lungs) are packed with proteins that bind up heme and hemoglobin, apparently to starve the bacterium. Despite this, how Mtb takes up heme is largely unknown, which makes it impossible to say how much heme acquisition matters for virulence.
Why it matters
With 3.4% of new and 18% of previously treated tuberculosis cases multidrug-resistant in 2024, new drug strategies are urgently needed. Because iron is essential to Mtb and heme is the largest host iron pool, the uptake proteins mapped here, including the PPE outer-membrane channels, the Dpp transporter and Rv0125, could become targets for drugs that starve the bacterium of iron rather than attacking pathways to which it is already resistant.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jeffrey Tornheim
Johns Hopkins University, MD·Medicine & Clinical Research
Determine how many MDR-TB patients in Mumbai carry resistance mutations that would rule out moxifloxacin, linezolid, bedaquiline, clofazimine or cycloserine, using next-generation sequencing directly from uncultured sputum.
Christina Leigh Stallings
Washington University in St Louis, MO·Microbiology & Immunology
Define how SPTLC2, the rate-limiting enzyme subunit for building sphingolipids, supports maintenance and monocyte-derived repopulation of alveolar macrophages during M. tuberculosis infection, using mice lacking Sptlc2 in CD11c+ lung cells.
Mushtaq Ahmed
University of Chicago, IL·Microbiology & Immunology
Determine whether bone morphogenetic protein (BMP) signaling, a lung development and repair pathway, is required to control Mycobacterium tuberculosis and prevent reactivation of latent TB.
The school
Oklahoma State University: 15 labs on PI Pages, $254M a year on research, 238 research doctorates a year.
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