UKZN’s TB Pathogenesis and Biomarker Discovery Research Group graduated four MSc students at the Autumn 2023 Graduation.

Ms Kynesha Moopanar, Ms Nkanyezi Masondo, Mr Michael Mbatha and Ms Asanda Nyide were awarded Master of Science degrees in Microbiology from UKZN’s College of Agriculture, Engineering and Science.

Moopanar’s research involved an in-depth examination of the metabolism of clinical strains of Mycobacterium tuberculosis (M. tb, which causes Tuberculosis [TB]) that are highly prevalent in KwaZulu-Natal, and how cholesterol may assist their continued survival in the lungs.

She said she always wanted to work with infectious diseases, adding that TB is still very much a threat and easing the burden of this disease in South Africa is an on-going goal.

Moopanar aims to become a fully-fledged research scientist and said she owed her success thus far to both of her grandmothers, ‘who lifted me up when I couldn`t lift myself – this one is for them.’  She praised UKZN for its academic excellence and unwavering support throughout her academic journey.

Masondo’s research focused on selecting and identifying Mycobacterium tuberculosis epitope biomarkers that bind specifically to the Human Leukocyte Antigen-E (HLA-E) receptor for recognition by the CD8+ T-cells specific receptors in vitro. She confirmed protein-protein interaction using molecular docking to demonstrate binding of selected epitopes to HLA-E receptor binding pockets. This enabled her to identify potential TB vaccine candidate epitopes for design and construction of a multi-epitope TB vaccine that would also be suitable for immunocompromised patients.

‘The significance of my research lies in its contribution to the search for new tools to end TB by 2035. It also lays the foundation for the development of a new TB vaccine capable of providing protection to immunocompromised individuals such as HIV and AIDS patients,’ she explained.

‘I grew up in an environment where many people (including me) lost loved ones to TB,’ said Masondo. ‘My curiosity around this disease was elevated and being in a science field was the only way to assist in answering most of my questions. My research excited me because I could finally understand the mechanisms of TB and contribute to the development of better treatment to prevent and control its spread.

‘Being able to identify vaccine candidates for a life-threatening disease has been very exciting and has instilled a desire to take this research to the next level where I can observe the immunological responses triggered by these vaccine candidates.’

She thanked her parents and grandmother for their support, encouragement and sacrifices, her supervisor Dr Thamsanqa Chiliza for sharpening her thinking and taking her work to another level, and her co-supervisor Dr Nontobeko Mvubu for her assistance and guidance.

Mbatha’s dissertation also focused on the development of a new TB vaccine. ‘The Bacillus Calmette-Guérin (BCG) vaccine is currently the only TB vaccine approved by the World Health Organization,’ he explained. ‘It was developed, however, to protect children from contracting TB. The majority of adults are still at risk of getting TB or dying from the disease owing to the lack of an effective vaccine against Mycobacterium tuberculosis, the causative agent of TB.

‘The research conducted by the TB research group is ground-breaking, with the potential to solve complex scientific problems and effect policy change,’ he said.  ‘I wanted to be a part of this group, make a scientific contribution and bring about positive change in society.’

Mbatha said his research was significant as robust TB preventative strategies such as the development of effective vaccines are urgently needed in a country where TB is such a health burden.

Commending his supervisors, Mbatha has set his sights on pursuing a PhD and becoming a top researcher

For Nyide, UKZN was a natural choice for her master’s research as she completed her undergraduate and honours degree at the Institution. Her topic was: Identification of Transcriptome Changes and Molecular Signatures in Macrophages during Infection by Clinical Strains of Mycobacterium tuberculosis.

‘Tuberculosis is a global health problem and one of the top 10 causes of death worldwide,’ she said. ‘In South Africa, it is undoubtedly the defining public health crisis of our time.

‘M. tuberculosis in immunocompromised persons is a major cause of mortality despite the treatment therapies that are available owing to adverse side effects and co-infections worldwide. Although our understanding of the pathogenesis and transmission dynamics has become more nuanced and prevention options have expanded, a cure or protective vaccine remains elusive.’

Nyide said it was desirable to establish biomarkers by developing novel pathways for drug discovery interactions that have anti M. tb transcription profiles. Bioinformatics tools and highly specialised molecular techniques like RNA sequences would aid the move towards possible vaccine development.

‘TB drug therapeutics has transformed M. tuberculosis from an inevitably fatal condition to a chronic, manageable disease in some settings,’ she said. ‘This transformation has yet to be realised in sub-Saharan Africa, which continues to bear a disproportionate burden of new TB infections and is impacted by increasing morbidity and mortality.’

Nyide’s study is significant as it reports on strain-specific gene expression and molecular signatures, as well as diverse cytokine profiles during early infection of macrophages through mRNA sequencing and cytokine analysis. The findings shed light on the strains’ ability to stimulate an early host immune response that can be implicated in the transmission dynamics of these strains within the South African population.

Nyide said she was motivated to conduct TB research because growing up she witnessed her brother pick up TB from an ill neighbour. ‘I wondered how it was transmitted to my brother, and my never ending curiosity prompted me to focus on TB research,’ she said.

Nyide plans to pursue a PhD in TB genomics research.

‘We are very proud of all the students for persevering through the pandemic until completion of their MSc studies,’ said Mvubu. ‘We wish them all the best in their future career endeavours and hope they will continue to contribute to the country’s knowledge economy and skills transfer.’

Words: Sally Frost

Photograph: Rajesh Jantilal