University of Cape Town (IDM)

Institute of Infectious Disease and Molecular Medicine (IDM)

Molecular Mycobacteriology Research Unit

Centre of Excellence for Biomedical TB Research

Member since 2020

Representative

Valerie Mizrahi PhD, Professor, Director and Full member

Team

• Digby Warner
• Melissa Chengalroyen
• Mandy Mason
• Timothy de Wet
• Sophia Gessner
• Sasha Lynch
• Audrey Jordaan

About

Situated on the health sciences campus of the University of Cape Town (UCT), the Institute of Infectious Disease and Molecular Medicine (IDM) is a cross-faculty postgraduate research enterprise where world-class scientists work together in more than 20 research groupings to tackle diseases of major importance in Africa through cutting-edge laboratory, clinical and population health research. The IDM uses research as the vehicle to develop indigenous scientific capacity and strives to influence health policy and practice by translating scientific discoveries and applying them in the community. Research conducted in the IDM has been particularly influential in the prevention and management of HIV and HIV-associated infections, the diagnosis, immunopathogenesis and management of tuberculosis (TB) and TB-IRIS, the prevention and immunopathology of COVID-19, the evolutionary virology of SARS-CoV-2, the discovery and evaluation of predictive biomarkers for progression to active TB, and the clinical evaluation of new TB vaccine candidates. TB comprises one of the IDM’s most prominent research themes, spanning the continuum from discovery to development and implementation of new tools for TB control.  Facilities for TB research in the IDM include a well-equipped BSL3 core facility which houses a super-resolution microscope and cell sorter and is fully capacitated for medium-throughput TB drug screening. 

Valerie Mizrahi (the IDM director) and Digby Warner participate in the TBDA through the Molecular Mycobacteriology Research Unit (MMRU), an extramural research unit of the SAMRC, which they jointly lead and is located within the IDM. Their group focuses on studying aspects of the physiology and metabolism of M. tuberculosis relevant to TB drug discovery, drug resistance, and the aerobiology of TB transmission. As TB biologists, they contribute to the TBDA by biologically profiling and elucidating the mechanisms of action of novel antimycobacterial agents. They have specialist expertise in mycobacterial genetics and chemical-genomics, and in the application of super-resolution microscopy, live-cell imaging, and flow cytometry TB research.  

Links

Valerie Mizrahi, Tackling big questions in tuberculosis: a TB biologist’s view from South Africa. Science talk presented at the Life Sciences Across the Globe Seminar series, August 5, 2020 (virtual)

Valerie Mizrahi, Planning for research impact: lessons from a decade as director of the IDM. Wolfson Memorial Lecture, University of Cape Town, November 22, 2021 (hybrid)

References

1. Abrahams, G. L.; Kumar, A.; Savvi, S.; Hung, A. W.; Wen, S.; Abell, C.; Barry, C. E.; Sherman, D. R.; Boshoff, H. I. M.; Mizrahi, V. Pathway-Selective Sensitization of Mycobacterium Tuberculosis for Target-Based Whole-Cell Screening. Chemistry & Biology 2012, 19 (7), 844–854. https://doi.org/10.1016/j.chembiol.2012.05.020.
2. Evans, J. C.; Trujillo, C.; Wang, Z.; Eoh, H.; Ehrt, S.; Schnappinger, D.; Boshoff, H. I. M.; Rhee, K. Y.; Barry, C. E.; Mizrahi, V. Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway of Mycobacterium Tuberculosis. ACS Infectious Diseases 2016, 2 (12), 958–968. https://doi.org/10.1021/ACSINFECDIS.6B00150.
3. Naran, K.; Moosa, A.; Barry, C. E.; Boshoff, H. I. M.; Mizrahi, V.; Warner, D. F. Bioluminescent Reporters for Rapid Mechanism of Action Assessment in Tuberculosis Drug Discovery. Antimicrobial Agents and Chemotherapy 2016, 60 (11). https://doi.org/10.1128/AAC.01178-16.
4. Moosa, A.; Lamprecht, D. A.; Arora, K.; Barry, C. E.; Boshoff, H. I. M.; Ioerger, T. R.; Steyn, A. J. C.; Mizrahi, V.; Warner, D. F. Susceptibility of Mycobacterium Tuberculosis Cytochrome Bd Oxidase Mutants to Compounds Targeting the Terminal Respiratory Oxidase, Cytochrome c. Antimicrobial Agents and Chemotherapy 2017, 61 (10). https://doi.org/10.1128/AAC.01338-17.
5. de Wet, T. J.; Winkler, K. R.; Mhlanga, M.; Mizrahi, V.; Warner, D. F. Arrayed Crispri and Quantitative Imaging Describe the Morphotypic Landscape of Essential Mycobacterial Genes. eLife 2020, 9. https://doi.org/10.7554/eLife.60083.
6. Chengalroyen, M. D.; Jordaan, A.; Seldon, R.; Ioerger, T.; Franzblau, S. G.; Nasr, M.; Warner, D. F.; Mizrahi, V. Biological Profiling Enables Rapid Mechanistic Classification of Phenotypic Screening Hits and Identification of KatG Activation-Dependent Pyridine Carboxamide Prodrugs With Activity Against Mycobacterium Tuberculosis. Frontiers in Cellular and Infection Microbiology 2020, 10. https://doi.org/10.3389/fcimb.2020.582416.
7. Evans, J. C.; Murugesan, D.; Post, J. M.; Mendes, V.; Wang, Z.; Nahiyaan, N.; Lynch, S. L.; Thompson, S.; Green, S. R.; Ray, P. C.; Hess, J.; Spry, C.; Coyne, A. G.; Abell, C.; Boshoff, H. I. M.; Wyatt, P. G.; Rhee, K. Y.; Blundell, T. L.; Barry, C. E.; Mizrahi, V. Targeting Mycobacterium Tuberculosis CoaBC through Chemical Inhibition of 4′-Phosphopantothenoyl- l -Cysteine Synthetase (CoaB) Activity. ACS Infectious Diseases 2021, 7 (6), 1666–1679. https://doi.org/10.1021/ACSINFECDIS.0C00904.
8. Chengalroyen, M. D.; Mason, M. K.; Borsellini, A.; Tassoni, R.; Abrahams, G. L.; Lynch, S.; Ahn, Y.-M.; Ambler, J.; Young, K.; Crowley, B. M.; Olsen, D. B.; Warner, D. F.; Barry, C. E.; Boshoff, H. I. M.; Lamers, M. H.; Mizrahi, V. DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in Mycobacterium Tuberculosis. bioRxiv 2021, 2021.10.27.466036. https://doi.org/10.1101/2021.10.27.466036.