Research Focus:

The Laboratory of Infectious Disease Metabolomics is focused on characterizing amongst others; Human Immunodeficiency virus (HIV) and Mycobacterium tuberculosis (TB)-induced metabolic alterations, through the development and application of state of the art metabolomics technologies and/or approaches.

Considering the extremely high prevalence of these infections in Sub-Sahara Africa, and South Africa in particular, the laboratory is perfectly situated for addressing this problem, not only with regards to its location and collaborations with various local and international pathology laboratories, clinics and other collaborative infectious disease institutions, but also with regards to its research relevance towards curbing 3rd world and worldwide infectious diseases problems.


Research Leaders:

Prof Du Toit Loots

Laboratory of Infectious Disease Metabolomics

Human Metabolomics

Building F3 – Biochemistry / Private Bag X 6001,Internal Box 269

North-West University

Potchefstroom

South Africa

Tel: 018 299 1818

E-mail: dutoit.loots@nwu.ac.za

 

Dr Aurelia Williams

Laboratory of Infectious Disease Metabolomics

Human Metabolomics

Building F3 – Biochemistry / Private Bag X 6001, Internal Box 269

North-West University

Potchefstroom

South Africa

Tel: 018 285 2542

E-mail: aurelia.williams.nwu.ac.za

 

Dr Shayne Mason

Laboratory of Infectious Disease Metabolomics

Human Metabolomics

Building F3 – Biochemistry / Private Bag X 6001, Internal Box 269

North-West University

Potchefstroom

South Africa

Tel: 018 285 2531

E-mail: nmr.nwu@gmail.com


 

General Contact:

Postal Address:

 

Private Bag X 6001

Potchefstroom

2520  

South Africa

Physical Address:

 

Mitochondria Research Laboratory 

Building F3 – Biochemistry   

North-West University 

Potchefstroom

General Contact Person:

 

Mrs Hettie Meyer – Secretary 

018 299 2307

hettie.meyer@nwu.ac.za

 

Active Researchers:

TB studies:

Technical Assistant:

  • Mrs Derylize Maasdorp

Post doc:

  • Dr Francois Taute

  • Dr Ilse Olivier

PhD:

  • Mrs Laneke Luies

  • Miss Fatima Janodien

  • Miss Leone Venter

MSc:

  • Miss Nadia Koen

  • Miss Christinah Mothswane

  • Miss Chante’ Venter

Hons:

  • Mrs Derylize Maasdorp

  • Zinandre’ Prinsloo

 

HIV studies:

PhD:

  • Miss Gontse Moutloatse

MSc:

  • Mr Emile Janse van Rensburg

Hons:

  • Mr Jacques-Frans

  • Mev Nicolene Odendaal


Funders:

                                                       


Collaborators:

Our collaborators and/or coinvestigators are as follows:

TB Studies:

  • Prof Nico Gey Van Pittius, NRF/DST Centre of Excellence for TB research, Stellenbosch University Faculty of Medicine, Tygerberg, Cape Town

  • Dr K. Ronacher, NRF/DST Centre of Excellence for TB research, Stellenbosch University Faculty of Medicine, Tygerberg, Cape Town

  • Prof Gerhard Walzl, NRF/DST Centre of Excellence for TB research, Stellenbosch University Faculty of Medicine, Tygerberg, Cape Town

  • Dr S. van Breda, Department of Internal Medicine, Division of Infectious Diseases, University of Pretoria

  • Prof Mark Nicol, Division of Medical Microbiology, Department of Clinical Laboratory Sciences
    And Institute of Infectious Disease and Molecular Medicine, UCT Faculty of Health Sciences, Cape Town

  • Prof Ron A. Wevers & Dr Udo F.H. Engelke, Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen,The Netherlands.

  • Prof A. Marceline Tutu van Furth, Department of Paediatric Infectious Diseases–Immunology and Rheumatology, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.

  • Prof Regan Solomons, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town.

 

HIV Studies:

  • Prof Thumbi Ndung'u, Director, HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

  • Prof Carina Mels, Hypertension in Africa Research Team (HART), Africa Unit for Transdisciplinary Health Research (AUTHeR), North-West University, Potchefstroom, South Africa.

  • Prof Carla Fourie, Hypertension in Africa Research Team (HART), Africa Unit for Transdisciplinary Health Research (AUTHeR), North-West University, Potchefstroom, South Africa.


History of the Research Group:

In 2006, Biopad, as subsidiary of the Technology Innovation Agency (TIA), was tasked with the establishment of ‘omics’ technology in South Africa. Through the initiatives of Prof Carolus Reinecke, the NWU biochemistry group was selected to host the metabolomics platform due to the extensive expertise of the group in metabolic analysis and profiling.  This fruitful partnership resulted in a significant investment by both Biopad and the NWU into the future of the biochemistry group. In 2007 the NWU also approved the establishment of the Centre for Human Metabolomics (CHM) as a centre of competence in accordance with the requirements of Biopad after an external evaluation was conducted in 2006.

To the end of 2010 Biopad, as well as various other subsidiaries was seeded into TIA which brought about a renewed intensified focus on metabolomics. It became clear that TIA would in future invest most of its funding in applied metabolomics research, meant to bridge the gap between basic research and commercialization. TIA committed to the establishment of a National Metabolomics Platform (NMP) to be hosted at the NWU and subsequently provide substantial funding for the future development of the facility including funding for equipment, operational expenses and investment in human capital. Construction of the facility that will host the platform commenced at the end of 2011 and was completed in September 2012.

In July 2015, a new research entity was established, the focus area: Human Metabolomics (HM), under the directorship of Prof Du Toit Loots, with its focus being basic and applied metabolomics and systems biology research, and that of the CHM, under the directorship of Prof Chris Vorster to commercialize the developed methodologies or research findings. These ventures are achieved together by TIA, the National Research Foundation (NRF), and other private funders. The functioning of these entities is totally dependent on its expertise and the highly specialised equipment. In 2008, TIA insisted on broadening this scope to diseases of high prevalence in Africa and globally, and subsequently Prof Du Toit Loots established the research programme “Metabolomics of Infectious and Acquired Diseases” within a new research institute in NWU, FHM. The HIV component was recently added to the research program following Dr Williams’ August 2016 appointment.


Research Background:

HIV, the causative agent of the acquired immunodeficiency syndrome (AIDS), impacts both on the immune and metabolic systems of its host. While combination antiretroviral therapy (cART) has been successfully administered to alleviate virus-induced effects and prolong the lifespan of infected individuals, the therapeutics augment virus-induced metabolic abnormalities. This has given rise to the development of HIV and/or cART- associated comorbidities, the mechanisms of which have to be elucidated.

In addition, HIV-infected patients typically progress to the AIDS stage in about eight years. But, individuals are heterogeneous in their response to HIV exposure and infection i.e. not everyone follows the typical eight-year survival trend. The heterogeneous responses have largely been attributed to host genetics while the role of the genes on metabolism and the subsequent role thereof on disease pathogenesis has lagged behind.

At the point of succumbing to AIDS, infected individuals are highly susceptible to opportunistic infections such as tuberculosis (TB), brought on by pathogens such as Mycobacterium tuberculosis (Mtb). HIV/TB co-infections and the development of multi-drug resistant TB is increasing at a rapid rate complicating diagnosis and treatment of the disease.


Research Objectives and Technologies used:

The research done in our laboratory is multidisciplinary with a special focus on using metabolomics research approaches to better characterize HIV and TB infections respectively, drug resistant TB strains, HIV/TB co-infections, disease pathogenesis, response to therapy and infection-associated comorbidities. It is our objective to ultimately develop faster, simpler and more sensitive diagnostic and prognostic tests for these conditions to facilitate disease management as well as the screening and/or development of improved anti-HIV/TB drug candidates.

The Laboratory of Infectious Disease Metabolomics at the NWU-Centre for Human Metabolomics, boasts Biosafety Level 3  (P3) analytical facilities where basic/cell/tissue culture and aseptic techniques can be practised. This world-class facility boasts expertise and infrastructure on par with other international metabolomics facilities.  Here, individuals develop skills regarding the handling and storing of infectious biomaterial. A state of the art GCxGC-TOFMS is located in the P3 Laboratory allowing for the ultimate analysis (regarding sensitivity and separation capacity) of infected samples or pathogenic organisms while they are metabolically active, which is not the case with other metabolomic / analytical laboratories.  The GCxGC-TOFMS is furthermore equipped with a multi-purpose sampler, allowing for automated solid phase extraction, solid phase micro extraction, dynamic headspace and thermal desorption.  Headspace-Thermal Desorption (HS-TD) is a highly versatile, sensitive and labour-saving sample preparation technique for the measurement of volatile and semi-volatile organic compounds (VOC and SVOC) and provides the ultimate sample introduction technology for GCxGC-TOFMS combining selective concentration enhancement with direct extraction into the carrier gas and efficient transfer/injection, all in one fully automated and labour saving package. The success of this unit is due to its extensive analytical infrastructure and additionally includes: gas chromatography mass spectrometry (GC-MS), liquid chromatography tandem mass spectrometry (LC-MSMS), liquid chromatography time of flight mass spectrometry (LC-TOFMS) (1 x TOF & 1 x QTOF), ion trap mass spectrometry, capillary electrophoresis (CE) and LC-diode array. In addition to the comprehensive array of MS-based instruments, a 500 MHz nuclear magnetic resonance (NMR) spectrometer was setup for dedicated biofluid analysis at the NWU-Centre for Human Metabolomics at the start of 2015. While less sensitive than its MS-counterparts, NMR technology is complementary and highly specific – allowing for greater coverage of the metabolome, and level one identification of metabolites. Complementing the advanced scientific equipment are the specialized staff, each with expertise in various facets of metabolomics analytical sample analysis on the above mentioned analytical apparatus, using any sample matrix, and then those individuals specializing in data analysis, data clean-up, data processing and statistical data analysis/bioinformatics.


Current Research Activities and Developments:

Metabolomics approaches are applied to HIV and/or TB-infected biomaterial to identify markers. These metabolic markers when interpreted in the context of a systems biology approach together with information attained through genomics, proteomics and transcriptomics analyses, are used to:

  • Inform on pathogen-host interactions, diseases mechanisms and disease pathogenesis

  • Facilitate the development of improved HIV/TB diagnostics and prognostics using patient collected sputum, blood and urine

  • Inform on infection-associated comorbidities

  • Aid in the screening of new anti-HIV/TB drug candidates –using metabolomics to elucidate mechanisms of action of drugs and host response to treatments (ultimately informing on rationale drug and vaccine design as well as the management of the disease).


Publications:

Prof Du Toit Loots’ publications (last 5 years)

  • I. Olivier, D.T. Loots. 2012. A metabolomics approach to characterise and identify various Mycobacterium species.  Journal of Microbiological Methods, 88: 419-426. Impact factor 2.2

  • I. Olivier, D.T. Loots. 2012. Altered fatty acid metabolism due to rifampicin-resistance conferring mutations in the rpoB gene of M. tuberculosis: mapping the potential of pharmaco-metabolomics for global health and personalized medicine. Omics: A Journal of Integrative Biology, 16 (11) 596-603. Impact factor 2.9

  • I. Olivier, D.T. Loots. 2012. A comparison of two extraction methods for differentiating and characterising various Mycobacterium species and Pseudomonas aeruginosa using GC-MS metabolomics.  African Journal of Microbiology Research: 6 (13): 3159-3172. Impact factor 0.5

  • R.J. Meissner-Roloff, R.M. Warren, D.T. Loots. 2012. A metabolomics investigation of a hyper- and hypo-virulent phenotype of Beijing lineage M. tuberculosis. Metabolomics, 8:1194-1203. Impact factor 4.5

  •  J.C. Schoeman, I. Du Preez, Du T. Loots. 2012. A comparison of four sputum pre-extraction preparation methods for identifying and characterising Mycobacterium tuberculosis using GCxGC-TOFMS metabolomics.  Journal of Microbiological Methods: 91: 301-311. Impact factor 2.2

  • I. Du Preez, Du T. Loots. 2013. Detection limit for differentiating between various Mycobacterium species and Pseudomonas aeruginosa using gas chromatography-mass spectrometry (GC-MS) metabolomics: A comparison of two extraction methods. African Journal of Microbiology Research. 79: 797-801. Impact factor 0.5

  •  Du.T. Loots., R.J. Meissner-Roloff, M. Newton-Foot, N.C. Gey van Pittius. 2013. A metabolomics approach exploring the function of the ESX-3 type VII secretion system of M. smegmatis. Metabolomics. 9: 631-641. Impact factor 4.5.

  • I. du Preez, Du T. Loots.  New metabolite markers from sputum implicating various adaptations of the host to M. tuberculosis, and vice versa. 2013. Tuberculosis. 93: 330-337. Impact Factor 3.5

  • L. de Villiers, Du T. Loots. (2013). Using metabolomics for elucidating the mechanisms related to tuberculosis treatment failure, Current Metabolomics, 1(4): 306-317.

  • M.C. Zatu, J.M. Van Rooyen, Du T. Loots, E. Wentzel-Viljoen, M. Greeff, A.E. Schutte. 2014. Self-reported alcohol intake is a better estimate of 5-year change in blood pressure than biochemical markers in low resource settings: The PURE study. J Hypertens. 32:749-755. Impact Factor 4.7

  • Du T Loots. 2014. An altered M. tuberculosis metabolome induced by katG mutations resulting in isoniazid-resistance. Journal of Antimicrobial Agents and Chemotherapy, 58 (4): 2144-2149. Impact Factor 4.8

  • I. du Preez, Du T. Loots.  2014. Can metabolomics improve tuberculosis diagnosis? Metabolomics, 10: 877-886 Impact Factor 4

  • C.C. Swanepoel and Du T. Loots, “The Use of Functional Genomics in Conjunction with Metabolomics for Mycobacterium tuberculosis Research,” Disease Markers, vol. 2014, Article ID 124218, 12 pages, 2014. doi:10.1155/2014/124218. Impact factor 2.2

  • M.C. Zatu, J.M.van Rooyen, Du T. Loots, M. Greeff, A.E. Schutte. 2015. A comparison of the cardiometabolic profile of black South Africans with suspected non-alcoholic fatty liver disease (NAFLD) and excessive alcohol use. Alcohol. 49 (2): 165-72. doi: 10.1016/j.alcohol.2014.11.002. IF 2.255

  • P.T. Pisa, H.H. Vorster, A. Kruger, B. Margetts, Du T. Loots. 2015. Association of Alcohol Consumption with Specific Biomarkers: A Cross-sectional Study in South Africa. Journal of Health, Population and Nutrition.   33 (1), 146-156. Impact Factor 1.4

  • Du T Loots. 2016. New insights into the survival mechanisms of rifampicin resistant tuberculosis. Journal of Antimicrobial Chemotherapy. 71, 655-660. doi:10.1093/jac/dkv406. Impact Factor 5.3

  • L. Venter, P. Jansen van Rensburg, Du T. Loots, A. Vosloo, J.Z. Lindeque. 2016. Untargeted metabolite profiling of abalone using gas chromatography mass spectrometry. Food Analytical Methods. 9(5):1254-1261. DOI 10.1007/s12161-015-0285-5. Impact Factor 2.2

  • L. Luies, Du T. Loots. 2016. Tuberculosis metabolomics reveals adaptations of man and microbe in order to outcompete and survive. Metabolomics. 12 (40): 1-9. Impact factor 3.7

  • Du T. Loots C.C. Swanepoel, M. Newton-Foot, Gey van Pittius, Nicolaas C. A. 2016. Metabolomics investigation of the function of the ESX-1 gene cluster in mycobacteria. Microbial Pathogenesis. 100: 268-275. Impact Factor 1.9

  • D.T. Loots. (2016). TB or not TB? Improving the understanding and diagnosis of TB through metabolomics, Biomarkers in Medicine. 10 (10): 1025-1028. Impact factor 2.2

 

Dr Aurelia Williams’ publications (last 5 years)

  • Llewellyn E. Jalbert, Adam Elkhaled, Joanna J. Phillips, Evan Neill, Aurelia Williams, Jason C. Crane, Marram P. Olson, Annette M. Molinaro, Mitchel S. Berger, John Kurhanewicz, Sabrina M. Ronen, Susan M. Chang & Sarah J. Nelson. Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma. Scientific Reports 7, Article number: 44792 (2017). doi:10.1038/srep44792

  • Aurelia Williams, Khanyisile Kgoadi, Francois Steffens, Paul Steenkamp and Debra Meyer (2014). UPLC-MS Metabonomics Reveals Perturbed Metabolites in HIV-Infected Sera. Current Metabolomics

  • Williams A, Steffens F, Reinecke C and Meyer D (2013). The Th1/Th2/Th17 cytokine profile of HIV-infected individuals: A multivariate cytokinomics approach, Cytokine, (61) 521-526.

  • Sitole L, Williams A, Meyer D (2013) Metabonomic analysis of HIV-infected biofluids, Mol Biosyst, (9)18 –28.

  • Williams A, Koekemoer G, Lindeque Z, Reinecke C and Meyer D (2012). Qualitative serum organic acid profiles of HIV infected individuals not on treatment, Metabolomics, Volume 8 (5) 808-818

  • Williams A and Meyer D (2009). Desferrioxamine as immunomodulatory agent during microorganism infection, Current Pharmaceutical Design, (15) 1261-1268.

 

Dr Shayne Mason’s publications (last 5 years)

  • Smuts, I., Van der Westhuizen, F.H., Louw, R., Mienie, L.J., Engelke, U.F., Wevers, R.A., Mason, S., Koekemoer, G. and Reinecke, C.J., 2013. Disclosure of a putative biosignature for respiratory chain disorders through a metabolomics approach. Metabolomics9(2), pp.379-391.

  • Mason, S., P Moutloatse, G., Marceline van Furth, A., Solomons, R., van Reenen, M., Reinecke, C. and Koekemoer, G., 2014. KEMREP: A new qualitative method for the assessment of an analyst’s ability to generate a metabolomics data matrix by gas chromatography–mass spectrometry. Current Metabolomics2(1), pp.15-26.

  • Mason, S., van Furth, A.M., Mienie, L.J., Engelke, U.F., Wevers, R.A., Solomons, R. and Reinecke, C.J., 2015. A hypothetical astrocyte–microglia lactate shuttle derived from a 1H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis. Metabolomics11(4), pp.822-837.

  • Mason, S., Reinecke, C.J., Solomons, R. and Van Furth, A., 2016. Tuberculous meningitis in infants and children: Insights from nuclear magnetic resonance metabolomics. South African Journal of Science112(3-4), pp.1-8.

  • Mason, S., Reinecke, C.J., Kulik, W., Van Cruchten, A., Solomons, R. and van Furth, A.M.T., 2016. Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid. BMC Infectious Diseases16(1), p.251.

  • Mason, S., van Furth, A.M.T., Solomons, R., Wevers, R.A., van Reenen, M. and Reinecke, C.J., 2016. A putative urinary biosignature for diagnosis and follow-up of tuberculous meningitis in children: outcome of a metabolomics study disclosing host–pathogen responses. Metabolomics12(7), pp.1-16.

  • van Aardt, W.J., le Roux, J.M., Lindeque, J.Z., Mason, S. and Louw, R., 2016. The effect of temperature on the respiration and metabolism of the African burrowing scorpion (Opistophthalmus latimanus). Comparative Biochemistry and Physiology Part D: Genomics and Proteomics20, pp.50-56.

  • Moutloatse, G.P., Bunders, M.J., van Reenen, M., Mason, S., Kuijpers, T.W., Engelke, U.F., Wevers, R.A. and Reinecke, C.J., 2016. Metabolic risks at birth of neonates exposed in utero to HIV-antiretroviral therapy relative to unexposed neonates: an NMR metabolomics study of cord blood. Metabolomics12(11), p.175.

  • Irwin, C., van Reenen, M., Mason, S., Mienie, L.J., Westerhuis, J.A. and Reinecke, C.J., 2016. Contribution towards a Metabolite Profile of the Detoxification of Benzoic Acid through Glycine Conjugation: An Intervention Study. PloS one11(12), p.e0167309.

  • Mason, S., 2017. Lactate shuttles in neuroenergetics — homeostasis, allostasis and beyond. Frontiers in Neuroscience, 11(43), 1-15.

  • Malatji, B.G., Meyer, H., Mason, S., Engelke, U.F., Wevers, R.A., van Reenen, M. and Reinecke, C.J., 2017. A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurology, 17(88), 1-15.

  • Mason, S., Reinecke, C.J., Solomons, R., Wevers, R.A. and Engelke, U.F., 2017. 1H NMR spectral identification of medication in cerebrospinal fluid of pediatric meningitis. Journal of Pharmaceutical and Biomedical Analysis, 143, pp.56-61.