Education and Training
2000 B.S., Biology and Chemistry, University of West Indies, Barbados
2005 Ph.D., Molecular Microbiology, University of Leeds, UK
2006- Postdoctoral Fellow, University of Tennessee HSC
Dr. Hurdle’s research centers on the discovery of novel approaches to treat antibiotic-resistant infections and elucidating molecular and physiological responses of bacteria to antimicrobials. Hurdle’s laboratory adopts a multi-disciplinary approach, involving: discovery of novel antimicrobials through phenotypic and enzyme-based screening of chemical libraries; characterizing the molecular action of novel antimicrobials; assessing antibiotic efficacy in animal models of disease; and interrogating the impact of genetic resistance on bacterial physiology and virulence. Notable achievements include the discovery of antimicrobial agents that are at various pre-clinical stages for treating Clostridium difficile infection, biofilm-mediated infections and Mycobacterium tuberculosis. A key concept from Hurdle’s research is that the bacterial membrane is an Achilles of recalcitrant bacteria, such as stationary phase cells and biofilms; these cell types display phenotypic resistance and cause infections to relapse after treatment. Through this concept, we are probing mechanisms of chemically induced cell death in C. difficile. We collaborate closely with medicinal chemists, structural biologists and pharmacologists, to achieve our goal of translating discoveries to human medicine.
- Feng L, Maddox MM, Alam MZ, Tsutsumi LS, Narula G, Bruhn DF, Wu X, Sandhaus S, Lee RB, Simmons CJ, Tse-Dinh YC, Hurdle JG, Lee RE, Sun D. Synthesis, Structure-Activity Relationship Studies, and Antibacterial Evaluation of 4-Chromanones and Chalcones, as Well as Olympicin A and Derivatives. J Med Chem. 2014 (Ahead of print, Oct 7, PMID: 25238443).
- Kumar M, Adhikari S., Hurdle, J.G. (2014) Action of nitroheterocyclic drugs against Clostridium difficile. Int. J. Antimicrob. Agents 44:314-9.
- Cherian, T. P., Wu, X., Maddox, M.M., Singh, A.P., Lee, R.E., Hurdle, J.G. (2014) Chemical modulation of the biological activity of reutericyclin: a membrane-active antibiotic from Lactobacillus reuteri. Sci Rep. 4:4721
- Wu X, Hurdle JG. (2014) The Clostridium difficile proline racemase is not essential for early logarithmic growth and infection. Can. J. Microbiol. 60:251-4
- Richard E. Lee, Julian G. Hurdle, Jiuyu Liu, Tanja Matt, Michael Scherman, Pavan Vaddady, Zhong Zheng, Jianjun Qi, David Bruhn, Rashid Akbergenov, Sourav Das, Dora B. Madhura, Ashit Trivedi, Maria-Cristina Villellas, Robin. B. Lee, Rakesh, Dianqing Sun, Michael R. McNeil, Jose A. Ainsa, Helena Boshoff, Bernd Meibohm, Erik C. Böttger, Anne J. Lenaerts. (2014) Spectinamides: a new class of semisynthetic anti-tuberculosis agents that overcome native drug efflux. Nat. Med. 20:152-8.
- Rakesh, Bruhn, D.F., Scherman, M.S., Woolhiser, L.K., Madhura, D.B., Maddox, M.M., Lee, R.B., Hurdle, J.G., McNeil, M.R., Lenaerts, A.J., Meibohm, B. and Lee, R.E. (2014) Pentacyclic nitrofurans with in vivo efficacy and activity against nonreplicating Mycobacterium tuberculosis. PLoS One. 9:e87909.
- Tsutsumi LS, Owusu YB, Hurdle JG, Sun D. Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review. Curr Top Med Chem. 14:152-75.
- Wu, X., Alam, X., Feng, L., Tsutsumi, L.S. Sun, D. and Hurdle J.G (2014) Prospects for flavonoid and related phytochemicals as nature-inspired treatments for Clostridium difficile infection. J. Appl. Microbiol. 116: 23-31.
- Wu X, Hurdle JG. (2013). Screening for a diamond in the rough. Chem Biol. 20(9):1091-2.
- Shen L, Maddox MM, Adhikari S, Bruhn DF, Kumar M, Lee RE, Hurdle JG, Lee RE, Sun D. (2013) Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents. J Antibiot (Tokyo). 66:319-25.
- Wu X, Cherian PT, Lee RE, Hurdle JG. (2013). The membrane as a target for controlling hypervirulent Clostridium difficile infections. J Antimicrob Chemother. 68:806-15.
- Sun D, Hurdle JG, Lee R, Lee R, Cushman M, Pezzuto JM. (2012). Evaluation of flavonoid and resveratrol chemical libraries rveals abyssinone II as a promising antibacterial lead. ChemMedChem. 7:1541-5.
- Brown JR, North EJ, Hurdle J.G., Morisseau C, Scarborough JS, Sun D, Korduláková J, Scherman MS, Jones V, Grzegorzewicz A, Crew RM, Jackson M, McNeil MR, Lee RE (). The structure-activity relationship of urea derivatives as anti-tuberculosis agents. Bioorg Med Chem. 9:5585-95
- Hurdle, J.G., Heathcott, A.E., Yang, L., Yan. B., Lee, R.E. (2011) Reutericyclin and related analogues kill stationary phase Clostridium difficile at achievable colonic concentrations. J Antimicrob Chemother; 66:1773-6.
- Hurdle, J.G., O'Neill, A.J., Chopra, I., Lee, R.E. (2011) Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nat. Rev. Microbiol. 9:62-75.
- Hevener, K., Yun, M.K., Qi, J., Kerr, I., Babaoglu, K., Hurdle, J., Balakrishna, K., White, S. and Lee, R. (2010) Structural studies of pterin-based inhibitors of dihydropteroate synthase. J. Med. Chem. 53:166-77.
- Budha, N.R., Lee, R., Hurdle, J.G., Lee, R.E. and Meibohm, B. (2009) Simple in vitro PK/PD model system to determine time-kill curves of drugs against Mycobacterium tuberculosis. Tuberculosis (Edinb); 89:378-85.
- Hurdle, J.G., Yendapally, R., Sun D and Lee, R.E. (2009) Evaluation of analogs of reutericyclin as prospective candidates for staphylococcal skin infections. Antimicrob. Agents Chemother. 53:4028-31.