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.
Get in touch with Adrie via firstname.lastname@example.org
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.
*High-resolution scanned images from the Steyn Group’s recent paper can be downloaded below by clicking on the thumbnail. All images from: Md. Aejazur Rahman, Bridgette M. Cumming, Kelvin Addicott, Hayden Pacl, Shannon Russell, Kievershen Nargan, Threnesan Naidoo, Pratistadevi K. Ramdial, John H. Adamson, Rui Wang, and Adrie J. C. Steyn. (2020) Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis. PNAS, In Press.
Figure 1. Spatial distribution of CSE, CBS and MPST in the human TB lung. Low power H&E demonstration of a tuberculosis cavity (A) and IHC staining of CSE (B), MPST (C) and CBS (D). Low power H&E demonstration of caseous necrotic granuloma (H) and IHC staining of CSE (I), MPST (J) and CBS (K).
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*High-resolution scanned images from the Steyn Group’s recent paper can be downloaded below by clicking on the thumbnail. All images from: Reddy VP, Chinta KC, Saini V, Glasgow JN, Hull TD, Traylor A, Rey-Stolle F, Soares MP, Madansein R, Rahman MA, Barbas C, Nargan K, Naidoo T, Ramdial PK, George JF, Agarwal A, Steyn AJC. (2018). Ferritin H Deficiency in Myeloid Compartments Dysregulates Host Energy Metabolism and Increases Susceptibility to Mycobacterium tuberculosis Infection. Front Immunol. 2018 May 3;9:860. doi: 10.3389/fimmu.2018.00860
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*High-resolution scanned images from the Steyn Group’s recent Cell Reports paper can be downloaded below by clicking on the thumbnail. All images from: Chinta KC, Rahman MA, Saini V, Glasgow JN, Reddy VP, Lever JM, Nhamoyebonde S, Leslie A, Wells RM, Traylor A, Madansein R, Siegal GP, Antony VB, Deshane J, Wells G, Nargan K, George JF, Ramdial PK, Agarwal A, Steyn AJC. Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis. Cell Reports. 2018 Nov 13;25(7):1938-1952.e5. doi: 10.1016/j.celrep.2018.10.073. PubMed PMID: 30428359; PubMed Central PMCID: PMC6250977.
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Meet the Team
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
Jared was awarded his PhD in 2017 while working in the Bioengineering Lab at AHRI. His PhD looked at drug resistance mechanisms of Mycobacterium tuberculosis using novel microfluidics technology. Currently he is a Postdoctoral Research fellow at AHRI in Dr Adrie Steyn’s group, where he is studying the effects of drugs on the Mycobacterium tuberculosis energy metabolism.
Collaborating PhD student
Camus Nimmo is a registrar in respiratory medicine from the UK. He has taken time out of training to study for a PhD at University College London and AHRI. He is investigating the role of minority genetic populations of Mycobacterium tuberculosis, found in sputum and lung tissue samples on the development of drug resistance, using next generation whole genome sequencing.
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.
Kerishka Rajkumar was awarded her honours from Stellenbosch University. At AHRI, her research focusses on the molecular basis of how TB becomes resistant to a wide variety of drugs, in the hope that this will provide much needed information that will aid the fight against drug-resistant TB.
Kievershen Nargan is qualified and registered with the HPCSA as a biomedical technologist (Histopathology). His work includes the reception, macroscopic appraisal and processing, microtome sections, histochemical staining (routine and special), immunohistochemistry as well as molecular biology of human lung specimens. Kievershen is also currently completing her Bachelor of Commerce degree.
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 Comrades Marathon medalist.
Gordon was awarded his PhD in Biochemistry from the University of Pretoria. His research has mostly focused on the application of molecular modelling to drug discovery (malaria, neurotransmission, coenzyme A biosynthesis). He has recently transitioned into image analysis and is interested in all aspects of computational biology and how best to apply them to disease research.
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.