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MSc (Biochemistry), North-West University, Potchefstroom Campus The synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) during co-infection of a host is well established. While this synergy is driven by immunological deterioration, the metabolic mechanisms that contribute to the associated disease burden experienced during HIV/TB co-infection remain poorly understood. Although antiretroviral therapy (ART) suppresses viral replication, these therapeutics give rise to metabolic disruptions and adaptations beyond that induced by infection. In this study, the serum cytokine and metabolic profiles of 9 untreated HIV/TB co-infected, 12 HIV/TB co-infected on ART, and 22 HIVnegative TB-positive patients, as well as 29 healthy controls, were measured and compared. A cytometric bead array kit was used for multiplexed cytokine measurements, and an untargeted two-dimensional gas chromatography time-of-flight mass spectrometry approach was used for metabolomics analyses. There was no significant difference between the cytokine levels of the diseased groups when compared to each other or the controls, however, the co-infected individuals were characterised by increased interleukin (IL)-6, and interferon-gamma (IFN-γ) when compared to the controls. The concomitant increase of cytokines typically classified as T helper cell type (Th) 1 or Th2, and as pro-inflammatory or immunoregulatory, suggests a failure of immunoregulation, resulting in an increased disease burden. Metabolites indicative of cachexia, damage of the intestinal mucosa and dysbiosis of the microbiome characterised co-infected individuals from the TB-positive population, while co-infected individuals were distinguished from healthy controls by similar alterations with the addition of more extensive amino acid changes. Loss of gut integrity and subsequent microbial translocation results in increased inflammation and immune/cytokine activation, culminating in a reduced appetite and malabsorption, which support the profile of exacerbated wasting in HIV/TB co-infected individuals. Treating HIV in the co-infected group revealed that some altered metabolites returned to values comparable to those of the healthy or the TB-positive population. However, it is unclear whether this represents a return to a more healthy state, as other metabolic alterations were exacerbated upon treatment. These results suggest that HIV augments the HIV-Mtb synergy, at least in part, through its detrimental effects on gut health, which in turn, affects energy availability. Masters

SUMMARY Clinical symptoms of active tuberculosis (TB) can range from a simple cough to more severe reactions, such as irreversible lung damage and, eventually, death, depending on disease progression. In addition to its clinical presentation, TB has been associated with several other disease-induced systemic complications, such as hyponatremia and glucose intolerance. Here, we provide an overview of the known, although ill-described, underlying biochemical mechanisms responsible for the clinical and systemic presentations associated with this disease and discuss novel hypotheses recently generated by various omics technologies. This summative update can assist clinicians to improve the tentative diagnosis of TB based on a patient’s clinical presentation and aid in the development of improved treatment protocols specifically aimed at restoring the disease-induced imbalance for overall homeostasis while simultaneously eradicating the pathogen. Furthermore, future applications of this knowledge could be applied to personalized diagnostic and therapeutic options, bettering the treatment outcome and quality of life of TB patients.

PhD (Biochemistry), North-West University, Potchefstroom Campus Although moderate physical activity is substantially beneficial to human health, continuous participation in endurance running (≥5 km), has been associated with various adverse physiological and immunological effects. Despite these effects, endurance running is still considered a popular global pass time that has rapidly evolved into a highly competitive sport, classified as either a half-marathon (21 km), marathon (42 km) or ultra-marathon (≥42 km). Considering that recovery is a key component in athletic performance, previous research approaches have been directed towards identifying more cost-effective, readily available recovery approaches, such as functional foods (beetroot, cherry, pomegranate, bananas, etc.). These foods, especially beetroot, are rich in antioxidants and possess potent radical scavenging properties, that may aid in the physiological and immunological post-training recovery of athletes. Despite the well-characterised nature of the aforementioned effects and the recovery thereof, very limited literature exists pertaining to the holistic metabolic adaptations that may arise due to participation in endurance races and how these may recover with and without the intervention of recovery aids. Since metabolomics not only elucidates the effects of an intervention at metabolic level, but also provides a representation or prediction of the organism’s phenotypic state at a specific point in time, it is an excellent research approach to fill these voids. Metabolomics is defined as the comprehensive identification and quantification of the small metabolites (

MSc (Biochemistry), North-West University, Potchefstroom Campus, 2018 Mycobacterium tuberculosis is estimated to infect approximately one-third of the world’s population, which can lead to an active, symptomatic disease called tuberculosis (TB), or to asymptomatic states, often referred to as latent TB infection. In 2015 alone, 10.4 million new TB cases were reported, resulting in an estimated 1.8 million deaths. Since the discovery of M. tuberculosis in 1882 by Robert Koch, a vast amount of genomics, proteomics and transcriptomics data have been generated, leading to our current understanding of M. tuberculosis and TB. Most of the data generated from studies used M. tuberculosis cultures; however, it is well-known that this organism’s metabolism and growth in culture differs greatly from growth in the human host, where many different growth mechanisms and energy substrates are preferentially used. Furthermore, very little research to date has focused on the adaptations of M. tuberculosis to the host’s defence mechanisms or growth environment, or for that matter, the host’s adaptations or altered metabolic state in response to the infectious pathogen. This is important since the pathophysiology of M. tuberculosis is directly linked to its metabolism and complex physiology, and to that of the host. Additionally, this pathogen can utilise numerous growth substrates, either by scavenging this from the host or via de novo biosynthesis, in order to ensure its own survival. Metabolomics has served well to expand the current knowledge of the disease and has contributed towards the improved diagnosis and treatment thereof, due to its unique capacity for identifying new disease biomarkers. Metabolomics is defined as the unbiased identification and quantification of the entire metabolome in a specific biological system, with the use of highly advanced analytical instruments, together with various statistical, computational and mathematical analyses. Metabolomics has enabled the identification of new metabolite markers in sputum, blood and urine from TB patients, describing novel M. tuberculosis metabolic pathways and host adaptations. Apart from their possible diagnostic applications, many of these new TB metabolite markers have contributed to the existing knowledge of the biology of the causative pathogen, including various underlying disease mechanisms related to M. tuberculosis drug resistance and virulence, as well as the mechanisms of TB drug action and related side-effects in the host. To date, however, very little data has been published on urine from TB patients, which can be considered an ideal sample matrix to identify markers associated with this host–pathogen interaction. Considering this, in this investigation, a combined semi-targeted liquid and gas chromatography mass spectrometry metabolomics approach was used to compare the urinary fatty acylcarnitines, amino acids and selected organic acids of active TB patients with that of healthy individuals, in order to better characterise the TB-induced alterations to the host metabolome. The generally elevated concentrations of the fatty acylcarnitines and amino acids are most likely due to TB-cachexia. However, the significantly elevated concentrations of arginosuccinate, asparate (and associated asparagine), ornithine (and associated proline and hydroxyproline) and glutamate (and associated glutamine) in particular, indicate a urea cycle abnormality, due to inhibition of N-acetylglutamate synthase by the accumulating propionyl-CoA, isovaleryl-CoA and methylmalonyl-CoA in TB patients. Furthermore, elevated propionylcarnitine, methylmalonate and methylcitrate in the TB patient urine are associated with a vitamin B12 deficiency, which deserves further investigation. Lastly, various metabolites indicative of lactic acidosis, ketoacidosis, oxidative stress and liver damage were identified in the urine of the TB patients Masters