Prof. Grüber, Gerhard
Professor
Phone: (65) 6316 2989
Email: [email protected]
Personal Lab Webpage: https://www.professorgerhardgruberlab.com
The elevated prevalence of drug resistant microorganisms worldwide has become one of the major public health threats of current times. The tuberculosis (TB)-causing mycobacterium Mycobacterium tuberculosis, non-tuberculous mycobacteria (NTM), or the life-threatening pathogen Acinetobacter baumannii are representatives of pan drug-resistant superbugs. While NTM are responsible for severe respiratory, skin and mucosal infections in humans A. baumannii causes infections of the skin and soft tissue, urinary tract infections, meningitis, bacteremia, and pneumonia. We are interested in relationships between the structure and mechanism(s) of mycobacterial enzymes related to bioenergetics, stress response and coenzyme A biosynthesis and of the oxidative phosphorylation pathway of A. baumannii. The team uses a variety of molecular biology, protein chemistry, structural, biochemical and biophysical approaches, paving the way for new structures, -targets, novel or improved inhibitors and lead compounds, whose potencies are studied on the pathogens.
Research Areas
Bioenergetics, Structural biology, Antimicrobial resistance, Target identification, Drug discovery
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PhD Student
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Research Fellow
- Ragunathan, P., Sielaff, H., Sundararaman, L., Biuković, G., Manimekalai, M.S.S., Singh, D., Kundu, S., Wohland, T., Frasch, W., Dick, T., and Grüber, G. “The Uniqueness of Subunit α of Mycobacterial F‑ATP Synthases: An Evolutionary Variant for Niche Adaptation.” Journal of Biological Chemistry 292 (2017): 11262–11279. https://doi.org/10.1074/jbc.M117.784959
- Hotra, A., Ragunathan, P., Ng, P.S., Seankongsuk, P., Harikishore, A., Sarathy, J.P., Saw, W.-G., Lakshmanan, U., Sae-Lao, P., Kalia, N.P., Shin, J., Kalyanasundaram, R., Anbarasu, S., Parthasarathy, K., Pradeep, C.N., Makhija, H., Dröge, P., Poulsen, A., Tan, J.H.L., Pethe, K., Dick, T., Bates, R.W., and Grüber, G. “Discovery of a Novel Mycobacterial F‑ATP Synthase Inhibitor and Its Potency in Combination with Diarylquinolines.” Angewandte Chemie International Edition 132 (2020): 13397–13406. https://doi.org/10.1002/anie.202002546
- Saw, W.-G., Leow, C.Y., Harikishore, A., Shin, J., Cole, M., Aragaw, W.W., Ragunathan, P., Hegde, P., Aldrich, C.C., Dick, T., and Grüber, G. “Structural and Mechanistic Insights into Mycobacterium abscessus Aspartate Decarboxylase PanD and a Pyrazinoic Acid‑Derived Inhibitor.” ACS Infectious Diseases 7 (2022): 1324–1335. https://doi.org/10.1021/acsinfecdis.2c00133
- Ragunathan, P., Sae-Lao, P., Hamela, C., Alcaraz, M., Krah, A., Poh, W.H., Pee, C.J.E., Lim, A.Y.H., Rice, S.A., Pethe, P., Bond, P.J., Dick, T., Kremer, L., Bates, R.W., and Grüber, G. “High Efficacy of the F‑ATP Synthase Inhibitor TBAJ‑5307 Against Non‑Tuberculous Mycobacteria In Vitro and In Vivo.” Journal of Biological Chemistry 300, no. 2 (2024): 105618. https://doi.org/10.1016/j.jbc.2023.105618
- Le, K.C.M., Wong, C.F., Müller, V., and Grüber, G. “Cryo‑EM Reveals Transition States of the Acinetobacter baumannii F1‑ATPase Rotary Subunits γ and ε, Unveiling Novel Compound Targets.” FASEB Journal 38 (2024): e70131. https://doi.org/10.1096/fj.202401629R