Project Grant R01AI198349

Federal Grant Award Summary

The University of Texas at Arlington received a $583,822 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), effective June 25, 2026 through May 31, 2031. The research project investigates bacterial modulation of host metabolism and immunity during infection, specifically examining how bacterial pathogens evade thymineless death (TLD)—a mechanism induced by anti-folate antibiotics that inhibit nucleotide synthesis. Using Listeria monocytogenes as a model system, the research will elucidate three key pathways: (1) the role of cyclic di-AMP (c-di-AMP) and the PII family protein PstA in TLD inhibition; (2) the host immune response through STING activation and interferon-beta production that triggers nucleotide salvage; and (3) bacterial surface nucleotidase mechanisms that convert host nucleic acids into accessible nucleotides for bacterial survival.

The deliverables from this project will advance understanding of antimicrobial resistance mechanisms and support the development of optimized therapeutic strategies against drug-resistant bacterial infections, particularly Listeria monocytogenes strains causing meningitis and refractory listeriosis. The research addresses critical knowledge gaps in thymineless death pathways and bacterial-host metabolic interactions, with potential applications to antimicrobial drug development and treatment optimization for infections resistant to conventional therapies.