Publications

Sanfetrinem, an oral β-lactam antibiotic repurposed for the treatment of tuberculosis.

Date Published: May 15, 2025
Tuberculosis (TB) is historically the world’s deadliest infectious disease. New TB drugs that can avoid pre-existing resistance are desperately needed. The β-lactams are the oldest and most widely used class of antibiotics to treat bacterial infections but, for a variety of reasons, they were largely ignored until recently as a…

How macrophage heterogeneity affects tuberculosis disease and therapy.

Date Published: May 7, 2025
Macrophages are the primary host cell type for infection by Mycobacterium tuberculosis in vivo. Macrophages are also key immune effector cells that mediate the control of bacterial growth. However, the specific macrophage phenotypes that are required for optimal immune control of M. tuberculosis infection in vivo remain poorly defined. There are…

Contribution of front-line, standard-of-care drugs to bactericidal responses, resistance emergence, and cure in murine models of easy- or hard-to-treat tuberculosis disease.

Date Published: May 7, 2025
By assessing the standard-of-care regimen for tuberculosis (TB) in BALB/c and C3HeB/FeJ mice, we demonstrate that rifampin, with or without pyrazinamide, is essential for an effective bactericidal response and suppression of resistance. Potency measurements in an lipid-rich model and a rabbit caseum assay recapitulate the significance of rifampin as a…

ACOD1-mediated lysosomal membrane permeabilization contributes to -induced macrophage death.

Date Published: March 25, 2025
(Mtb) primarily infects macrophages. In vitro without antibiotics, wild-type Mtb hastens death of the macrophages, but the processes leading to rapid cell death are not well understood. Our earlier work indicated that the death of Mtb-infected mouse macrophages in vitro is markedly exacerbated by induction of interferon-β (IFN-β) [L.

Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of .

Date Published: March 13, 2025
() infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host-derived lipids to maintain infection, the role of macrophage lipid processing on the bacteria’s ability to access the intracellular lipid pool remains undefined. We utilized a CRISPR-Cas9 genetic approach to…

Candidate transmission survival genome of .

Date Published: March 11, 2025
(Mtb), a leading cause of death from infection, completes its life cycle entirely in humans except for transmission through the air. To begin to understand how Mtb survives aerosolization, we mimicked liquid and atmospheric conditions experienced by Mtb before and after exhalation using a model aerosol fluid (MAF) based…

Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection.

Date Published: March 4, 2025
Successful tuberculosis therapy requires treatment with an unwieldy multidrug combination for several months. Thus, there is a growing need to identify novel genetic vulnerabilities that can be leveraged to develop new, more effective antitubercular drugs. Consequently, recent efforts to optimize tuberculosis (TB) therapy have exploited (Mtb) chemical genetics to identify…

A Physiologically Relevant In Vitro Model of Nonreplicating Persistent Mycobacterium tuberculosis in Caseum.

Date Published: March 1, 2025
Tuberculosis (TB) remains one of the leading infectious causes of death worldwide. Persistent bacterial populations in specific microenvironments within the host hamper efficient TB chemotherapy. Caseum in the necrotic core of closed granulomas and cavities of pulmonary TB patients can harbor high burdens of drug-tolerant Mycobacterium tuberculosis (MTB) bacilli, making…
Courtesy of the U.S. National Library of Medicine