• The main goal of Dr Adrie JC Steyn’s research group is to understand the mechanisms whereby Mycobacterium tuberculosis (M. tuberculosis) persist for decades without causing disease, to then suddenly explode.

    The Steyn Group is currently working on several projects centered 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.). Understanding the immunometabolism of TB and how M. tuberculosis reprograms host energy metabolism are also areas of interest in the Steyn laboratory. Lastly, the Steyn lab is interested in pulmonary TB, specifically the 3D structure of the human TB granuloma using micro-and nano computed tomography (CT).
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 Mycobacterium tuberculosis senses host Interferon-γ via the membrane protein MmpL10Communications Biology.  5. 2022
    2022 A high-resolution 3D atlas of the spectrum of tuberculous and COVID-19 lung lesionsEMBO Molecular Medicine.  14. 2022
    2022 HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway.eLife.  11. 2022
    2022 Omicron infection enhances Delta antibody immunity in vaccinated personsNature.  607:356-359. 2022
    2022 Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Ad26.CoV2.S Vaccination in People Living With Human Immunodeficiency Virus (HIV)Clinical Infectious Diseases.  75:E857-E864. 2022
    2022 Similar Antibody Responses Against Severe Acute Respiratory Syndrome Coronavirus 2 in Individuals Living Without and with Human Immunodeficiency Virus on Antiretroviral Therapy during the First South African Infection WaveClinical Infectious Diseases.  75:E249-E256. 2022
    2022 Mycobacterium tuberculosis DosS binds H2S through its Fe3+ heme iron to regulate the DosR dormancy regulonRedox Biology.  52. 2022
    2022 A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plateseLife.  11. 2022
    2022 Author Correction: The immunoregulatory landscape of human tuberculosis granulomas (Nature Immunology, (2022), 23, 2, (318-329), 10.1038/s41590-021-01121-x)Nature Immunology.  23:814. 2022
    2022 A Feedback Regulatory Loop Containing McdR and WhiB2 Controls Cell Division and DNA Repair in MycobacteriamBio.  13. 2022
    2022 The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysisThe Lancet Microbe.  3:e265-e273. 2022
    2022 Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralizationNature.  602:654-656. 2022
    2022 The immunoregulatory landscape of human tuberculosis granulomasNature Immunology.  23:318-329. 2022
    2021 Aggregated Mycobacterium tuberculosis Enhances the Inflammatory ResponseFrontiers in Microbiology.  12. 2021
    2021 A Rapid Drug Resistance Genotyping Workflow for Mycobacterium tuberculosis, Using Targeted Isothermal Amplification and Nanopore SequencingMicrobiology Spectrum.  9. 2021
    2021 Erratum: Host bioenergetic parameters reveal cytotoxicity of antituberculosis drugs undetected using conventional viability assays (Antimicrobial Agents and Chemotherapy (2021) 65:10 (e00932-21) DOI: 10.1128/AAC.00932-21)Antimicrobial Agents and Chemotherapy.  65. 2021
    2021 HIV status alters disease severity and immune cell responses in beta variant sars-COV-2 infection waveeLife.  10. 2021
    2021 Host bioenergetic parameters reveal cytotoxicity of antituberculosis drugs undetected using conventional viability assaysAntimicrobial Agents and Chemotherapy.  65. 2021
    2021 Micro-computed tomography analysis of the human tuberculous lung reveals remarkable heterogeneity in three-dimensional granuloma morphologyAmerican Journal of Respiratory and Critical Care Medicine.  204:583. 2021
    2021 Mycobacterium tuberculosis causes a leaky blood-brain barrier and neuroinflammation in the prefrontal cortex and cerebellum regions of infected mice offspringInternational Journal of Developmental Neuroscience.  81:428-437. 2021
    2021 Mycobacterium tuberculosis h2s functions as a sink to modulate central metabolism, bioenergetics, and drug susceptibilityAntioxidants.  10. 2021
    2021 Water-soluble tocopherol derivatives inhibit SARS-CoV-2 RNA-dependent RNA polymerase. 2021
    2021 Host immunity increases Mycobacterium tuberculosis reliance on cytochrome bd oxidasePLoS Pathogens.  17. 2021
    2021 Mycobacterium tuberculosis H2S functions as a sink to modulate central metabolism, bioenergetics, and drug susceptibility 2021
    2021 Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasmaNature.  593:142-146. 2021
    2021 Mycobacterium tuberculosis-induced maternal immune activation promotes autism-like phenotype in infected mice offspringInternational Journal of Environmental Research and Public Health.  18. 2021
    2021 Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lungJournal of Clinical Investigation.  131. 2021
    2021 Heme oxygenase-1 as a pharmacological target for host-directed therapy to limit tuberculosis associated immunopathologyAntioxidants.  10:1-18. 2021
    2021 Dual inhibition of the terminal oxidases eradicates antibiotic-tolerant Mycobacterium tuberculosisEMBO Molecular Medicine.  13. 2021
    2021 Use of Telepathology to Facilitate COVID-19 Research and Education through an Online COVID-19 Autopsy Biorepository.Journal of Pathology Informatics.  12:48. 2021
    2021 Use of telepathology to facilitate COVID-19 research and education through an online COVID-19 autopsy biorepositoryJournal of Pathology Informatics.  12. 2021
    2020 Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosisNature Communications.  11. 2020
    2020 Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesisNature Communications.  11. 2020
    2020 The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on TuberculosisFrontiers in Cellular and Infection Microbiology.  10. 2020
    2020 Relevance of the Warburg Effect in Tuberculosis for Host-Directed TherapyFrontiers in Cellular and Infection Microbiology.  10. 2020
    2020 Formation of Lung Inducible Bronchus Associated Lymphoid Tissue Is Regulated by Mycobacterium tuberculosis Expressed DeterminantsFrontiers in Immunology.  11. 2020
    2020 Comprehensive Examination of the Mouse Lung Metabolome following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry ApproachJournal of Proteome Research.  19:2053-2070. 2020
    2020 Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis 2020
    2020 Differential skewing of donor-unrestricted and γδ T cell repertoires in tuberculosis-infected human lungsJournal of Clinical Investigation.  130:214-230. 2020
    2020 New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosisPLoS Pathogens.  16. 2020
    2019 Compromised Metabolic Reprogramming Is an Early Indicator of CD8+ T Cell Dysfunction during Chronic Mycobacterium tuberculosis InfectionCell Reports.  29:3564-3579.e5. 2019
    2019 Erratum: Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis (Cell Reports (2018) 25(7) (1938–1952.e5), (S2211124718316772), (10.1016/j.celrep.2018.10.073))Cell Reports.  28:3286. 2019
    2019 Publisher Correction: Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis (Nature, (2019), 570, 7762, (528-532), 10.1038/s41586-019-1276-2)Nature.  572:E10. 2019
    2019 Group 3 innate lymphoid cells mediate early protective immunity against tuberculosisNature.  570:528-532. 2019
    2019 Remembering the host in tuberculosis drug developmentJournal of Infectious Diseases.  219:1518-1524. 2019
    2019 Integrating environmental health and genomics research in Africa: Challenges and opportunities identified during a Human Heredity and Health in Africa (H3Africa) Consortium workshopAAS Open Research.  2. 2019
    2018 Accessible and distinct decoquinate derivatives active against Mycobacterium tuberculosis and apicomplexan parasitesCommunications Chemistry.  1. 2018
    2018 Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human TuberculosisCell Reports.  25:1938-1952.e5. 2018
    2018 Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophageseLife.  7. 2018
    2018 Arylvinylpiperazine amides, a new class of potent inhibitors targeting QcrB of mycobacterium tuberculosismBio.  9. 2018
    2018 Host-pathogen redox dynamics modulate Mycobacterium tuberculosis pathogenesisFEMS Immunology and Medical Microbiology.  76. 2018
    2018 2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and Mycobacterium tuberculosis: Structure-Activity Relationships, Mechanism of Action and Absorption, Distribution, Metabolism, and Excretion CharacterizationACS Infectious Diseases.  4:954-969. 2018
    2018 RbpA and σB association regulates polyphosphate levels to modulate mycobacterial isoniazid-toleranceMolecular Microbiology.  108:627-640. 2018
    2018 Ferritin H deficiency in myeloid compartments dysregulates host energy metabolism and increases susceptibility to Mycobacterium tuberculosis infectionFrontiers in Immunology.  9. 2018
    2018 Role of Ergothioneine in Microbial Physiology and PathogenesisAntioxidants and Redox Signaling.  28:431-444. 2018
    2017 Erratum: Correction: Mycobacterium tuberculosis arrests host cycle at the G1/S transition to establish long term infection (PLoS pathogens (2017) 13 5 (e1006389))PLoS Pathogens.  13:e1006490. 2017
    2017 Mycobacterium tuberculosis arrests host cycle at the G1/S transition to establish long term infectionPLoS Pathogens.  13. 2017
    2017 Susceptibility of Mycobacterium tuberculosis cytochrome bd oxidase mutants to compounds targeting the terminal respiratory oxidase, cytochrome cAntimicrobial Agents and Chemotherapy.  61. 2017
    2016 The emerging role of gasotransmitters in the pathogenesis of tuberculosisNitric Oxide: Biology and Chemistry.  59:28-41. 2016
    2016 Mycobacterial WhiB6 Differentially Regulates ESX-1 and the Dos Regulon to Modulate Granuloma Formation and Virulence in ZebrafishCell Reports.  16:2512-2524. 2016
    2016 Turning the respiratory flexibility of Mycobacterium tuberculosis against itselfNature Communications.  7. 2016
    2016 Host-directed therapies for infectious diseases: current status, recent progress, and future prospects.Lancet Infectious Diseases.  16:e47-e63. 2016
    2016 Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosisCell Reports.  14:572-585. 2016
    2016 Attenuated heme oxygenase-1 responses predispose the elderly to pulmonary nontuberculous mycobacterial infections 2016
    2015 Host-directed therapies for tackling multi-drug resistant tuberculosis: Learning from the pasteur-bechamp debatesClinical Infectious Diseases.  61:1432-1438. 2015
    2015 Metabolic plasticity of central carbon metabolism protects mycobacteria 2015
    2015 Regulation of ergothioneine biosynthesis and its effect on Mycobacterium tuberculosis growth and infectivityJournal of Biological Chemistry.  290:23064-23076. 2015
    2015 Towards host-directed therapies for tuberculosisNature Reviews Drug Discovery.  14:511-512. 2015
    2014 Exposure to cigarette smoke impacts myeloid-derived regulatory cell function and exacerbates airway hyper-responsivenessLaboratory Investigation.  94:1312-1325. 2014
    2014 The physiology and genetics of oxidative stress in mycobacteriaMicrobiology Spectrum.  2. 2014
    2013 S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosisAmerican Journal of Respiratory and Critical Care Medicine.  188:1137-1146. 2013
    2012 Environmental heme-based sensor proteins: Implications for understanding bacterial pathogenesisAntioxidants and Redox Signaling.  17:1232-1245. 2012
    2012 Heme oxygenase-1 promotes granuloma development and protects against dissemination of mycobacteriaLaboratory Investigation.  92:1541-1552. 2012
    2012 Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivoMolecular Microbiology.  85:1148-1165. 2012
    2012 Iron sulfur cluster proteins and microbial regulation: Implications for understanding tuberculosisCurrent Opinion in Chemical Biology.  16:45-53. 2012
    2012 Mycobacterium tuberculosis WhiB3: A novel iron-sulfur cluster protein that regulates redox homeostasis and virulenceAntioxidants and Redox Signaling.  16:687-697. 2012
    2011 A screen to identify small molecule inhibitors of protein-protein interactions in mycobacteriaAssay and Drug Development Technologies.  9:299-310. 2011
    2011 Redox homeostasis in mycobacteria: the key to tuberculosis control?Expert Reviews in Molecular Medicine.  13. 2011
    2010 Conservation of structure and protein-protein interactions mediated by the secreted mycobacterial proteins EsxA, EsxB, and EspAJournal of Bacteriology.  192:326-335. 2010
    2010 Reductive stress in microbes: Implications for understanding mycobacterium tuberculosis disease and persistenceAdvances in Microbial Physiology.  57:43-117. 2010
    2009 Mycobacterium tuberculosis WhiB3 Maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage responsePLoS Pathogens.  5. 2009
    2008 Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulonJournal of Biological Chemistry.  283:18032-18039. 2008
    2007 A partner for the resuscitation-promoting factors of Mycobacterium tuberculosisMolecular Microbiology.  66:658-668. 2007
    2007 Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor 2007
    2007 Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival 2007
    2006 Dissecting virulence pathways of Mycobacterium tuberculosis through protein-protein association 2006
    2003 Interaction of the sensor module of Mycobacterium tuberculosis H37Rv KdpD with members of the Lpr familyMolecular Microbiology.  47:1075-1089. 2003
    2003 Cloning and characterization of a second α-amylase gene (LKA2) from Lipomyces kononenkoae IGC4052B and its expression in Saccharomyces cerevisiaeYeast.  20:69-78. 2003
    2002 Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth 2002
    2000 Characterization of the Mycobacterium tuberculosis iniBAC promoter, a promoter that responds to cell wall biosynthesis inhibitionJournal of Bacteriology.  182:1802-1811. 2000
    1999 Recent developments in mycobacterial researchCurrent Opinion in Infectious Diseases.  12:415-424. 1999
    1996 Cloning, mapping and characterization of a genomic copy of the Lipomyces kononenkoae alpha-amylase-encoding gene (LKA1).Yeast.  12:925-937. 1996
    1996 Cloning, mapping and characterization of a genomic copy of the Lipomyces kononenkoae α-amylase-encoding gene (LKA1)Yeast.  12:925-937. 1996
    1995 Cloning, sequence analysis and expression in yeasts of a cDNA containing a Lipomyces kononenkoae α-amylase-encoding geneGene.  166:65-71. 1995
    1995 Characterization of a novel α-amylase from Lipomyces kononenkoae and expression of its gene (LKA1) in Saccharomyces cerevisiae 1995
    1995 Expression of human p450c17 as an export protein in saccharomyces cerevisiaeEndocrine Research.  21:289-295. 1995
    1993 Regional sequence homologies in starch-degrading enzymes 1993
    1993 Expression and secretion of Bacillus amyloliquefaciens α-amylase by using the yeast pheromone α-factor promoter and leader sequence in Saccharomyces cerevisiaeApplied and Environmental Microbiology.  59:1253-1258. 1993
    1991 Co-expression of a Saccharomyces diastaticus glucoamylase-encoding gene and a Bacillus amyloliquefaciens α-amylase-encoding gene in Saccharomyces cerevisiaeGene.  100:85-93. 1991


    Year Title Altmetric
    2020 The Analysis of Mycobacterium tuberculosis-Induced Bioenergetic Changes in Infected Macrophages Using an Extracellular Flux Analyzer.  161-184. 2020
    2015 The physiology and genetics of oxidative stress in mycobacteria.  297-322. 2015
    2013 Protein-protein interaction in the-omics era: Understanding Mycobacterium tuberculosis function.  79-106. 2013

    Research Overview

  • Tuberculosis
  • Principal Investigator On

  • Advanced Genotypic and Phenotypic Monitoring of Drug Resistant TB to Improve TB Treatment Outcomes  awarded by ALBERT EINSTEIN COLLEGE OF MEDICINE
  • Carbon Monoxide and Mycobacterium Tuberculosis Persistance  awarded by Burroughs Wellcome Fund
  • Cigarette Smoke and Drug Resistant Tuberculosis  awarded by American Lung Association
  • Fostering International Collaboration between US-Based Institutions and K-RITH at the University of Kwazulu-Natal in Durban, South Africa  awarded by Hughes (Howard) Medical Institute
  • Heme Oxygenase–1 and the Bioenergetic Threshold of Latent TB and HIV Co-Infection  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Hydrogen Sulfide and Tuberculosis Disease  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Immunometabolism of M. Tuberculosis/HIV co-infection  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Interplay Between the Mtb Electron Transport Chain and Carbon Metabolism  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Mechanism of Mycobacterium Tuberculosis Persistence  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Metabolic Reprogramming of T Cell Energy Metabolism in Tuberculosis and HIV  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Metabolic Reprogramming of T Cell Energy Metabolism in Tuberculosis and HIV  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Real Time Measurement of Host Bioenergetics During Mycobacterium Tuberculosis Infection  awarded by DOD - ARMY MEDICAL RESEARCH ACQUISITION ACTIVITY
  • Role of WhiB3 in M. tuberculosis Virulence  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Target and Non-target Based Resistance to Bedaquiline in South Africa  awarded by SEFAKO MAKGATHO HEALTH SCIENCES UNIVERSITY
  • UAB - AHRI agreement for assignment of Dr Adries Steyn as a Scientist in Residence  awarded by AFRICA HEALTH RESEARCH INSTITUTE
  • Education And Training

  • Doctor of Philosophy in Microbiology, Stellenbosch University 1995
  • Full Name

  • Andries Steyn