Professor Adrie Steyn is a member of AHRI Faculty, and heads up a lab at the institute. He also retains a position and a research programme at the University of Alabama at Birmingham (UAB). He has a background in molecular genetics, with specific in-depth training and expertise in Mycobacterium tuberculosis (M. tuberculosis) virulence and pathogenesis using different animal models. Adrie did his PhD in yeast genetics at Stellenbosch University, and went on to postdoctoral positions at the Albert Einstein College of Medicine and Harvard University, where he studied the genetic mechanisms of M. tuberculosis virulence and persistence. He joined the Department of Microbiology at UAB in 2003. In 2011 he joined the KwaZulu-Natal Research Institute for TB-HIV (K-RITH) as its first principal investigator.
Adrie has laid the groundwork for developing novel tools and approaches for studying M. tuberculosis redox homeostasis during infection and studying the effect of NO, CO and hypoxia on M. tuberculosis persistence in vivo. His team has more recently discovered a novel mechanism of action of the antimycobacterial drugs bedaquiline, clofazimine and Q203, which targets energy metabolism in M. tuberculosis. He has inaugurated a formal collaboration with the cardiothoracic surgical team at the Inkosi Albert Luthuli Central Hospital and leads efforts for the Human Lung Project; established to collect resected lung tissue samples from TB patients.
Click here for a full list of publications.
The main goal of Dr Adrie Steyn’s research group is to understand the mechanisms whereby Mycobacterium tuberculosis (M. tuberculosis) persist for decades without causing disease, to then suddenly explode.
M. tuberculosis is the bacterium that causes TB in the lungs. Despite years of investigation and research, scientists and health practitioners today are still struggling to control and eradicate the TB epidemic. This is especially true when we try to combat persistent bacilli (the bacteria that continue to survive in the host in the presence of drugs). Persistence has been a major problem in M.tuberculosis management due to a limited understanding of the nature and mechanism of persisters. During persistence, tuberculosis enters a metabolically shutdown state which makes it difficult for anti-TB drugs to penetrate the waxy cell wall material.
The Steyn Group is currently working on several projects centred on host gasotransmitters such as nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S), and M. tuberculosis redox homeostasis and bioenergetics, the role it plays in latency and persistence of the mycobacterium inside the human host, and how this information can be translated into clinical uses. The mouse model for TB, as well as freshly resected human TB lung tissue, are routinely used by the Steyn group. The research group also uses extracellular metabolic flux analysis technology to measure the change in oxygen consumption rate of mycobacteria and infected host cells under different extracellular conditions (pH, carbon source, etc.). The long-term goal is to examine the mechanisms whereby M. tuberculosis reprograms host energy metabolism. The lab also investigates how this technology can be used in anti-tuberculosis drug and clinical isolate susceptibility screens.
Meet the Team
Postdoctoral Research Fellow
Bridgette Cumming received her PhD in Biochemistry from the University of KwaZulu-Natal in Pietermaritzburg, where she investigated the effects of antimalarial drugs and malaria pigment (β-haematin) on monocyte function. Her research at AHRI focusses on how mycobacterial infection skews the bioenergetics and metabolism of the host cell in order to establish disease.
Postdoctoral Research Fellow
Mohammed Aejazur Rahman received his BSc degree in Biotechnology and completed his Masters in Biological Science at the Indian Institute of Science, Bangalore. Aejaz’s current work focusses on host-pathogen interactions and signalling mechanisms during TB infection in the mouse model and in human lung tissue. He is also studying immunological responses mediated through soluble secretory antigens of M.tb that target the nuclei of host cells in the mouse model.
Postdoctoral Research Fellow
Dirk Lamprecht received his PhD in Bio-organic Chemistry from University of Stellenbosch. Dirk is currently involved with several projects centred on M.tb redox homeostasis and bioenergetics. He is also exploiting extracellular flux analysis technology to examine the change in oxygen consumption rate of mycobacteria under different extracellular conditions, and how this technology can be used in anti-TB drug and clinical isolated susceptibility screens.
Postdoctoral Research Fellow
Shannon was awarded her PhD from the University of British Columbia. Her PhD work examined the role of antibiotic use in early life, its impact on the gastrointestinal microbiome and how gut microbes affect susceptibility to gut and lung inflammatory diseases. Shannon is interested in understanding the role that nutrition and ultimately cellular metabolism plays in the progression of TB disease. She is also working on a collaborative project with University of California, Los Angeles, characterising the epigenetic landscape of the human TB lung.
Tawanda graduated with a BSc in Biochemistry and Chemistry summa cum laude (UKZN), a BSc Honours in Medicinal Chemistry summa cum laude (Rhodes University) and a Master of Medical Science degree summa cum laude (UKZN). His Masters work focused on the development of high through put research platforms and scalable diagnostic solutions using microfluidics technology. Tawanda is interested in understanding the interplay between metabolism and immunity in pulmonary TB, and how pharmacological intervention targeting immunometabolism could boost protective anti-TB immunity and improve clinical outcomes.
Tafara Kunota holds a BSc degree in Computational Physics and a BSc Honours degree in Physics, both awarded Summa Cum Laude by UKZN. He joined K-RITH’s bioengineering lab for his Masters, where he created and patented a unique automated point-of-care microfluidic fluid handling device. Tafara is interested in understanding the mechanisms responsible for drug resistance in TB.
Kelvin Addicott did his honours in Biochemistry and Genetics and his Masters in Biochemistry at the University of KwaZulu-Natal. Kelvin is currently assisting various research projects being done in the Steyn Lab, with a primary focus on the extracellular flux analyser. He also helps with BSL2 and BSL3 upkeep and administrative duties.
Rukaya Asmal completed her Honours in Medical Microbiology at the Nelson R Mandela School of Medicine with a molecular biology based TB project. She went on to do her Masters at the Centre of Excellence for Biomedical TB Research in Johannesburg. Rukaya is currently in charge of the Steyn Lab’s lung resection study, including collection and storage of tissue. Her other duties include BSL2 and BSL3 upkeep, administrative duties, as well as maintenance of strains in the lab.
Information Systems Technician
Kapongo Lumamba has a BSc Degree in Computer Science and is currently completing his Honours degree in Computing. His work involves web applications design and development, database development and maintenance, photography and graphic design and post mortem documentation to name just a few. Kapongo is also Comrade Marathon medalist.
Selected Recent Publications
Yong Wang, Tong Huan Jin, Aisha Farhana, Jason Freeman, Kim Estell, Jaroslaw Zmijewski, Amit Gaggar, Victor Thannickal, Lisa Schwiebert, Steyn AJC and Jessy Deshane. Exposure to cigarette smoke impacts myeloid-derived regulatory cell function and exacerbates airway hyper-responsiveness. Lab Invest. (2014) Dec;94(12):1312-25.
Zumla A, Chakaya J, Hoelscher M, Ntoumi F, Rustomjee R, Vilaplana C, Yeboah-Manu D, Rasolof V, Munderi P, Singh N, Steyn AJC et al. Towards host-directed therapies for tuberculosis. Nat Rev Drug Discov. (2015) Aug;14(8):511-2.
Cumming BM and Steyn AJC. Metabolic plasticity of central carbon metabolism protects Mycobacteria. Proc Natl Acad Sci USA. (2015) Oct 27;112(43):13135-6.
Saini V, Cumming BM, Guidry L, Lamprecht D, Adamson JH, Reddy VP, Chinta KC, Mazorodzo J, Glasgow JN, Richard-Greenblatt M, Gomez-Velasco A, Bach H, Av-Gay Y, Eoh H, Rhee K and Steyn AJC. Ergothioneine maintains redox and bioenergetic homeostasis essential for drug susceptibility and virulence of Mycobacterium tuberculosis. Cell Reports. (2016) 14(3):572-85. PMC4732560.
Lamprecht, D. A., Finin, P. M., Rahman, M. A., Cumming, B. M., Russell, S. L., Jonnala, S. R., Adamson, J. H., & Steyn, A. J. (2016). Turning the respiratory flexibility of Mycobacterium tuberculosis against itself. Nat Commun, 7, 12393. doi: 10.1038/ncomms12393.