Meenal Datta, Laura E Via, Véronique Dartois, Danielle M Weiner, Matthew Zimmerman, Firat Kaya, April M Walker, Joel D Fleegle, Isaac D Raplee, Colton McNinch, Maksym Zarodniuk, Walid S Kamoun, Changli Yue, Ashwin S Kumar, Sonu Subudhi, Lei Xu, Clifton E Barry, Rakesh K Jain
Host-directed therapies (HDTs) represent an emerging approach for bacterial clearance during tuberculosis (TB) infection. While most HDTs are designed and implemented for immuno-modulation, other host targets-such as nonimmune stromal components found in pulmonary granulomas-may prove equally viable. Building on our previous work characterizing and normalizing the aberrant granuloma-associated vasculature, here we demonstrate that FDA-approved therapies (bevacizumab and losartan, respectively) can be repurposed as HDTs to normalize blood vessels and extracellular matrix (ECM), improve drug delivery, and reduce bacterial loads in TB granulomas...
April 2, 2024: Proceedings of the National Academy of Sciences of the United States of America