Growing up in Cape Town, Adrie Steyn did not think he would work on TB. In 1994, he moved to the USA to finish his PhD in yeast genetics at Albert Einstein College of Medicine in New York. While there, he met HHMI Investigator Bill Jacobs, who studies TB at Einstein, and Barry Bloom, former dean of the Harvard School of Public Health.
Jacobs’ and Bloom’s enthusiasm for researching TB was inspiring. Steyn started doing a bit of reading and soon he was hooked. After doing a postdoctoral fellowship with Bloom at Einstein and Harvard, Steyn became a professor at the University of Alabama at Birmingham (UAB), where he studies how the bacterium that causes TB protects itself against the host’s immune system.
Professor Steyn established his lab at K-RITH in 2011, and retains a position and a research programme at UAB. At K-RITH he has inaugurated a formal collaboration with the cardiothoracic surgical team at the Inkosi Albert Luthuli Central Hospital in Durban, and leads efforts for the Human Lung Project; established to collect resected lung tissue samples from TB patients.
Get in touch with the Prof Steyn via email@example.com
The main goal of the Steyn Lab’s research 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 and contributes significantly to global mortality. 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, making it difficult for anti-TB drugs to penetrate the waxy cell wall material.
The Steyn lab 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 laboratory. Our 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. We also investigate how this technology can be utilised in anti-tuberculosis drug and clinical isolate susceptibility screens.
Meet the Team
POSTDOCTORAL RESEARCH FELLOW
Dirk Lamprecht completed a four year BSc degree at Stellenbosch University with Chemistry, Biochemistry and Genetics as major subjects. Dirk was introduced to TB research while completing his BSc Honours in Medical Biochemistry at the University of Stellenbosch’s DST/NRF Centre for Excellence in Biomedical TB Research, headed by Professor Paul van Helden. He continued with M. tuberculosis drug and enzymatic assay development research whilst completing his MSc (cum laude) as well as PhD in Bio-organic Chemistry under the supervision of Dr Anwar Jardine and Prof Erick Strauss respectively. Both his MSc and PhD thesis focused on the M. tuberculosis mycothiol biosynthetic pathway of five enzymes and the essential molecule, mycothiol, they produce. From his PhD research, a novel enzymatic 96-well plate assay for MshB – the third mycothiol biosynthetic enzyme, was developed which will streamline the high throughput screening of compounds against this enzyme. Dirk is currently involved with several projects centred on M.tb redox homeostasis and bioenergetics – the role it plays in latency and persistence of the mycobacterium inside the human host, and how what he learns can be translated into clinical uses. He is also exploiting extracellular flux analysis technology to examine the change in oxygen consumption rate of mycobacteria under different extracellular conditions (pH, carbon source, etc.), and how this technology can be used in anti-tuberculosis drug and clinical isolated susceptibility screens.
Terrence Jones is from Magee, Mississippi, in the USA. His undergraduate studies were in Biochemistry at the University of Mississippi, and he is currently completing medical school at the University of Tennessee Health Science Centre. He has previously done work in cellular metabolism in Dr Scott Ballinger’s lab at the University of Alabama, using extracellular flux analysis technology. Terrence is currently working as an HHMI Medical Fellow in K-RITH’s Steyn Lab. His project uses extracellular flux analysis technology to investigate the effects of tuberculosis infection on the metabolism of infected host macrophages and the effects of different drugs on the metabolism of Mycobacterium tuberculosis.
POSTDOCTORAL RESEARCH FELLOW
Shannon was awarded her PhD at the University of British Columbia (UBC) in Vancouver, Canada, in 2014. At UBC, she worked under Dr Brett Finlay, a well-known investigator in the field of enteric pathogenesis. 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. She published 11 peer-reviewed articles during her PhD and has presented her work at a number of international conferences. She is passionate about gut microbes, infectious diseases and global health. Shannon joined Adrie Steyn’s lab in 2015 as a postdoctoral research fellow. She 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.
Rukaya Asmal was born and bred in Durban, and did her undergraduate degree in Microbiology and Biochemistry at UKZN’s Westville campus. She attended K-RITH’s mycobacterial genetics course in her third year, which sparked a passion for TB research. Rukaya completed her Honours in Medical Microbiology at the Nelson R Mandela School of Medicine with a molecular biology based TB project. She then went on to do her Masters at the Centre of Excellence for Biomedical TB Research in Johannesburg, under the supervision of Prof Bavesh Kana. 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. She has also taken over experiments from students who have left K-RITH.
Kelvin Addicott did his honours in Biochemistry and Genetics and his Masters in Biochemistry at the University of KwaZulu-Natal, Pietermaritzburg. Kelvin says he has always had an interest in infectious diseases and wanted to be directly involved in researching the diseases that continue to have such a devastating impact on South Africa. 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.
POSTDOCTORAL RESEARCH FELLOW
Bridgette Cumming was born in Zimbabwe, but raised and schooled in South Africa. She 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. Bridgette initially qualified as a chemist. After four years in the chemical industry, she embarked on research in infectious diseases – specifically malaria – investigating signal transduction in the parasite, malaria diagnostics and drug discovery at the University of Witwatersrand and the University of Pretoria. Amidst the postgraduate studies, Bridgette was also involved in generating monoclonal antibodies for rapid immunochromatographic diagnostic kits for malaria using Hybridoma technology at National Bioproducts Institute in Pinetown. K-RITH presented an opportunity to diversify her infectious disease research and contribute towards furthering our understanding of the debilitating HIV-TB co-epidemic present in KZN. Bridgette’s research focusses on how mycobacterial infection skews the bioenergetics and metabolism of the host cell in order to establish disease. Metabolic Flux analysis is used to give a measure of basal respiration and glycolysis and parameters, such as spare respiratory capacity, glycolytic reserve, ATP turnover of mycobacterial infected macrophages relative to those parameters of uninfected cells. Chemically reversing the bioenergetics of the infected cell back to that of a healthy cell might enable the macrophage to eliminate the mycobacteria and provide novel strategies for conjunctive TB therapy.
POSTDOCTORAL RESEARCH FELLOW
Mohammed Aejazur Rahman was born and raised in Bhagalpur, a city situated on the southern bank of the river Ganges in the Indian state of Bihar. He received his BSc degree in Biotechnology and completed his Masters in Biological Science at the Indian Institute of Science, Bangalore. He joined the National Centre for Cell Science during his PhD, where he characterized TlyA, a Mycobacterium tuberculosis (M.tb) protein. He found that TlyA is a dual functionality protein, which has hemolysin as well as a ribosomal RNA methyltransferase activity. During his PhD, Aejaz received a fellowship from CSIR (from the government of India). In early 2010, he joined the Immunology group at ICGEB in New Delhi, for his postdoctoral training. At ICGEB, his field of study included mycobacterial pathogenesis and associated immunological responses in the mouse model. He has characterized a molecular mechanism of mycobacterial transmigration from the phagosome to the cytosol of the macrophage during tuberculosis (TB) infection. Aejaz’s current work focusses on host-pathogen interactions and signalling mechanisms during TB infection in the mouse model and in human lung tissue. M.tb has been shown to manipulate the host machinery to create a hostile environment within macrophages, the cells involved in the destruction and eradication of pathogens. He is therefore specifically interested in studying mycobacterial secretory proteins and other biomolecules which alter host bioenergetic pathways within the mitochondria and gene regulation inside the host nuclei. 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.
Turning the respiratory flexibility of Mycobacterium tuberculosis against itself Nat Commun, 7, 12393. doi:10.1038/ncomms12393
Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosis Cell Rep, 14(3), 572-585. doi:10.1016/j.celrep.2015.12.056
Host-Directed Therapies for Tackling Multi-Drug Resistant Tuberculosis: Learning From the Pasteur-Bechamp Debates. Clin Infect Dis. 2015 Nov 1;61(9):1432-8. doi: 10.1093/cid/civ631. Epub 2015 Jul 28.
Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity. J Biol Chem. 2015 Sep 18;290(38):23064-76. doi: 10.1074/jbc.M115.648642. Epub 2015 Jul 30.
Towards host-directed therapies for tuberculosis Nat Rev Drug Discov. 2015 Aug;14(8):511-2. doi: 10.1038/nrd4696. Epub 2015 Jul 17.