Adrie Steyn

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.

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Adrie Steyn

Steyn Group

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.

The group is also currently working on understanding the 3D architecture and spectrum of disease of TB infected human lung. The combination of multiple 2D and 3D imaging modalities (histology, spatial-omics, micro-computed tomography) applied to tissue from human autopsies and resected lung allows a far more comprehensive understanding of infection. The goal is to combine molecular, histological and anatomical signatures of TB infection in 3D to improve prevention and treatment.

*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). 


Figure 1A                                       Figure 1B

Figure 1C                                     Figure 1D

Figure 1H                                     Figure 1I

Figure 1J                                      Figure 1K


*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



Figure 2G                                              Figure 2H


Figure 8                                                 Figure 9


*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.



Figure S1                                            Figure S2A


Figure S2BC                                      Figure S2DEFG


Figure S3ABC                                   Figure S3D


Figure S4AB                                    Figure S4C

Figure S4F

Meet the Team

Bridgette Cumming - Steyn Group

Bridgette Cumming

Research associate

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.

Jared Mackenzie - Steyn Group

Jared Mackenzie

Lab supervisor

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. Jared has also been a Postdoctoral Research fellow at AHRI in Dr Adrie Steyn’s group, where he was studying the effects of drugs on the Mycobacterium tuberculosis energy metabolism.

Kievershen Nargan - Steyn Group

Kievershen Nargan

Pathology technologist

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 his Bachelor of Commerce degree.

Kapongo Lumamba  - Steyn Group

Kapongo Lumamba

3D imaging data curator

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 a Comrades Marathon medalist.

Gordon Wells  - Steyn Group

Gordon Wells

Research associate

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.

Threnesan Naidoo - Steyn Group

Threnesan Naidoo

Specialist Research Pathologist (Forensic)

Prof Threnesan Naidoo is a specialist pathologist (forensic) with formal training and a special interest in medical law, bio-ethics & human rights. His academic affiliations are in the faculty of medicine & health sciences at Walter Sisulu University in Mthatha, Eastern Cape, where he is professor and acting head of department of forensic & legal medicine as well as part-time professor in the division of anatomical pathology, department of laboratory medicine & pathology. His unique background in diagnostic autopsy pathology across the public and private health sectors in South Africa has enabled the acquisition of an impressive tissue cohort for research at AHRI. He has also established a free autopsy service to promote collaborative, tissue-based research into the complex pathogenesis and sequelae of TB and HIV disease.

Delon Naicker - Steyn Group

Delon Naicker

PhD Student

Delon completed an undergraduate degree majoring in chemistry and microbiology followed by an honours degree in microbiology through UNISA. He then did a masters degree in medical science at UKZN, working with HIV. His current PhD project aims to characterise the protein signature of active and latent TB-infected lesions.

Selected Recent Publications

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.

Wells G, Glasgow JN, Nargan K, Lumamba K, Madansein R, Maharaj K, Perumal LY, Matthew M, Hunter RL, Pacl H, Peabody Lever JE, Stanford DD, Singh SP, Bajpai P, Manne U, Benson PV, Rowe SM, le Roux S, Sigal A, Tshibalanganda M, Wells C, du Plessis A, Msimang M, Naidoo T, Steyn AJC. A high-resolution 3D atlas of the spectrum of tuberculous and COVID-19 lung lesions. EMBO Mol Med. 2022 Nov 8;14(11):e16283. doi: 10.15252/emmm.202216283. Epub 2022 Oct 26. PMID: 36285507; PMCID: PMC9641421.

Pacl HT, Chinta KC, Reddy VP, Nadeem S, Sevalkar RR, Nargan K, Lumamba K, Naidoo T, Glasgow JN, Agarwal A, Steyn AJC. NAD(H) homeostasis underlies host protection mediated by glycolytic myeloid cells in tuberculosis. Nat Commun. 2023 Sep 6;14(1):5472. doi: 10.1038/s41467-023-40545-x. PMID: 37673914; PMCID: PMC10482943.

Kunota TTR, Rahman MA, Truebody BE, Mackenzie JS, Saini V, Lamprecht DA, Adamson JH, Sevalkar RR, Lancaster JR Jr, Berney M, Glasgow JN, Steyn AJC. Mycobacterium tuberculosis H2S Functions as a Sink to Modulate Central Metabolism, Bioenergetics, and Drug Susceptibility. Antioxidants (Basel). 2021 Aug 13;10(8):1285. doi: 10.3390/antiox10081285. PMID: 34439535; PMCID: PMC8389258.

Cumming BM, Baig Z, Addicott KW, Chen D, Steyn AJC. Host Bioenergetic Parameters Reveal Cytotoxicity of Antituberculosis Drugs Undetected Using Conventional Viability Assays. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0093221. doi: 10.1128/AAC.00932-21.

Wells G, Glasgow JN, Nargan K, Lumamba K, Madansein R, Maharaj K, Hunter RL, Naidoo T, Coetzer L, le Roux S, du Plessis A, Steyn AJC. Micro-Computed Tomography Analysis of the Human Tuberculous Lung Reveals Remarkable Heterogeneity in Three-dimensional Granuloma Morphology. Am J Respir Crit Care Med. 2021 Sep 1;204(5):583-595. doi: 10.1164/rccm.202101-0032OC. PMID: 34015247; PMCID: PMC8491258.