Research
The Baughn Lab primarily focuses on tuberculosis drug discovery. We apply a variety of approaches in molecular biology, chemical biology, biochemistry and infection biology to understand fundamental mechanisms that govern resistance and susceptibility of Mycocbacterium tuberculosis to antimicrobial agents. We are interested in advancing the understanding of existing drugs, such as pyrazinamide and para-aminosalicylic acid (see below) and in identifying novel targets and small molecules for development of new antitubercular agents. Research activities in the Baughn Lab are supported by funds from the National Institute of Allergy and Infectious Diseases, Global Health Innovative Technology Fund and the University of Minnesota.
The Impact of Pyrazinamide on Metabolism in Mycobacterium tuberculosis (R01AI123146) - A project focused on solving the bewildering antitubercular activity of one of the cornerstones of modern tuberculosis therapy.
Targeting trans-Translation to Kill M. tuberculosis Non-Replicating Persister Cells (R01AI158706) - A collaboration with Dr. Ken Keiler of the Pennsylvania State University, focused on exploiting an essential ribosome rescue pathway for discovery of novel anti-tubercular agents.
Biomimetic Peptide Aerosols for Rapid Clearance of Pulmonary Tuberculosis (R01AI165996) - A collaboration with Dr. Scott Medina of the Pennsylvania State University, focused on development of rapidly bactericidal antimicrobial peptides that uniquely target the mycobacterial cell envelope.
Identification of novel dual-acting bactericidal drug targets against Mycobacterium tuberculosis - A collaboration with Dr. Yusuke Minato of Fujita Health Universityaims to identify novel targets for antitubercular drugs that can rapidly kill the bacilli through dual-acting mechanisms.
Overcoming Pyrazinamide Resistance with Pyrazinoate-Cephalosporin Conjugates (R21AI144501) – A joint pursuit with long-time collaborator, organic-medicinal chemist, and lab-neighbor Dr. Courtney Aldrich in the UMN Microbiology Research Facility.
Pyrazinamide action against Mycobacterium tuberculosis
Pyrazinamide (PZA) is a cornerstone antimicrobial drug used exclusively for the treatment of tuberculosis (TB) and is considered an irreplaceable component of standard first-line short-course therapy for drug-susceptible TB and second-line treatment regimens for multidrug-resistant TB. Despite over 60 years of research on PZA and its crucial role in current and future TB treatment regimens, the mode of action of this unique drug remains unclear. We are insterested in understanding mechanisms for PZA action, modulation of PZA susceptibility and resistance, and outlooks for future research and drug development.
Basis of para-Aminosalicylic Acid Susceptibility and Resistance in Mycobacterium tuberculosis
para-Aminosalicylic acid (PAS) entered clinical use in 1946 as the second exclusive drug for the treatment of tuberculosis (TB). Despite the long history of PAS usage, an understanding of the molecular and biochemical mechanisms governing the susceptibility and resistance of M. tuberculosis to this drug has lagged behind that of most other TB drugs. We aim to understand the basis of the susceptibility and resistance of M. tuberculosis to PAS to revitalize this and other antimicrobial agents for use in the global effort to eradicate TB.