UKZN and UNIZULU Researchers Discover Proteins to Fight Parasitic Disease
Researchers at UKZN and the University of Zululand (UNIZULU) have discovered three new classes of detoxification proteins from a human pathogen that causes a serious gastrointestinal disease.
UKZN’s Dr Thandeka Khoza and UNIZULU’s Professor Khajamohiddin Syed began the research following time they spent together which prompted exploration of opportunities for increased collaboration.
Khoza and Syed developed the rationale for the project, which examined the human pathogen Cryptosporidium that can cause the diarrheal disease cryptosporidiosis. Widespread throughout the world, cryptosporidiosis is one of the most common causes of waterborne disease, a leading cause of zoonotic parasitic disease - neglected forms of which constitute a global health burden - and a leading cause of death in children under the age of five.
For immunocompromised patients, cryptosporidiosis becomes life-threatening as it can spread from the gastrointestinal tract to sites including the gall bladder, biliary tract, pancreas, and pulmonary system.
Examining proteins they surmised could aid in fighting the disease, Khoza and Syed explained that living organisms on earth, from microbes to human beings, contained proteins that aid them in detoxification of foreign or harmful compounds they came into contact with in their environments.
‘One of these protein families is known as Glutathione Transferases (GSTs),’ said Khoza. ‘GSTs are diverse multifunctional proteins involved in cellular defence and detoxification in organisms and help pathogens to alleviate chemical and environmental stress, making them a drug target in fighting all kinds of pathogens.’
UKZN Biochemistry master’s student Ms Mbalenhle Mfeka started work on the project under the supervision of Khoza and Syed, first attending the 2019 Conference on Genomics, Proteomics and Metabolomics hosted by UNIZULU where a workshop equipped her with suitable research tools and mentorship from Khoza, Syed and other international bioinformatics researchers.
Mfeka began by performing genome data mining, annotation, phylogenetic and structural analysis of GSTs in Cryptosporidium species. Delineating the three new classes they found in this exercise as Vega (?), Gamma (?) and Psi (?), the researchers’ structural analysis of the GSTs revealed that the Vega class possesses a unique structure not described before.
According to Syed, this is a novel protein distinct from others, constituting fundamental research that opens new doors to drug discovery.
‘The discovery of these three new GST classes from South African researchers is a great contribution to GST research to the world,’ said Syed.
Khoza and Syed praised Mfeka for her hard work, dedication and perseverance during the study, highlighting the importance of this achievement for the field of bioinformatics in South Africa, a scarce skill area still developing in Africa.
This work has been published* in the prestigious Scientific Reports peer-reviewed journal. Khoza and Syed are corresponding authors, with Dr Ikechukwu Achilonu of the University of the Witwatersrand, Professor José Martínez-Oyanedel of the Universidad de Concepción in Chile, and Dr Wanping Chen of the University of Göttingen in Germany.
The researchers are currently working on deducing the structure of these new GST proteins and designing drugs to fight the effects of Cryptosporidium species.
Words: Christine Cuénod
Photographs: Christine Cuénod and Supplied