University of Minnesota
MICaB Graduate Program
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Current Students

Kordus
Shannon Kordus

E-mail:kordu003@umn.edu

Thesis Advisor: Anthony Baughn

Year entered: 2013

Degrees received:
B.S., University of Wisconsin, LaCrosse, WI, 2010
M.S., Boston University ,Boston, MA, 2013

Honors and awards:

  • MICaB Student Service Award 2016
  • MICaB Student Rep 2016-present
  • 3 Minute Thesis People’s Choice Award 2016
  • Young Scientist Travel Award 2016
  • Mycobacteria Research Lab’s Outstanding Poster 2016


Research:
Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for an estimated 1.5 million deaths annually. Although an effective treatment regimen exists, its implementation is challenging because it involves a minimum of six months of therapy with drugs that are associated with adverse reactions. These factors contribute to complications that have been implicated in the emergence of drug-resistant strains of M. tuberculosis. para-Aminosalicylic acid (PAS), is used to treat drug-resistant M. tuberculosis infections. PAS is thought to disrupt folate metabolism by inhibition of dihydrofolate reductase (DfrA), although the precise
mechanism for inhibition is still unresolved. We have shown that PAS is bioactivated to hydroxyl-dihydrofolate and which we found inhibits DfrA via a slow tight binding mechanism. The ability of PAS to disrupt folate metabolism is supported by the identification of molecular resistance mechanisms associated with mutation of genes involved in folate metabolism, namely folC (encoding dihydrofolate synthase) and thyA (encoding a non-essential thymidylate synthase). The biochemical mechanism(s) that govern PAS resistance associated with these mutations is still unknown. We have shown that genes involved in para-aminobenzoic acid (PABA) synthesis are up-regulated in folC resistant mutants suggesting that increased PABA biosynthesis maybe the biochemical basis for FolC linked resistance. Elucidating the mechanisms that govern the biochemical susceptibility and resistance of M. tuberculosis to existing anti-tubercular agents will facilitate the discovery of new therapeutic approaches to shorten treatment times and counter drug-resistance.

Publications:

  • Minato, Y., Thiede, J., Kordus, S.L., McKlveen, E., Turman, B.J., and Baughn A. 2015. Mycobacterium tuberculosis folate metabolism and the mechanistic basis for para-aminosalicylic acid susceptibility and resistance. Antimicrobial Agents and Chemotherapy. 59:5097-106.
  • Thiede, J.M., S. L. Kordus, B. J. Turman, J. A. Buonomo ,C. C. Aldrich, Y. Minato and A. D. Baughn. 2016. Targeting intracellular p-aminobenzoic acid production potentiates the anti-tubercular action of antifolates. (Submitted).