Africa Health Research Institute

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