Discovery of Proteins to Fight Parasitic Disease

Researchers at  the University of Zululand (UNIZULU) and the University of KwaZulu-Natal (UKZN)   have collaborated on research that details their discovery of three new classes of detoxification proteins from a human pathogen that causes a serious gastrointestinal disease.

Professor Khajamohiddin Syed from UNIZULU and Dr Thandeka Khoza from UKZN and conceived of this research after a short visit between the institutions prompted exploration of opportunities for increased research collaboration.

Prof Syed and Dr Khoza 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 amongst 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 that they surmised could aid in fighting the disease, Khoza and Syed explained that living organisms on earth, from microbes to human beings, contain proteins that aid them in detoxification of foreign or harmful compounds they come into contact with in their environments.

‘One of these proteins families are 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.’

UNIZULU hosted a Conference in 2019 on Genomics, Proteomics and Metabolomics where a workshop equipped a UKZN Biochemistry master’s student Mbalenhle Mfeka , a with suitable research tools and mentorship from Prof Syed and Dr Khoza. Ms Mbalenhle Mfeka took on work on the project under the supervision of Prof Syed and Dr Khoza.

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 (ϑ), Gamma (γ) and Psi (ψ), the researchers’ structural analysis of the GSTs revealed that the Vega class possess a unique structure not described before.

According to Prof  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 from South Africa to the world,’ said Syed.

Both the academics Prof Syed and Dr Khoza  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 that is still developing in Africa.

This work has been published* in the prestigious Scientific Reports peer-reviewed journal; Khoza and Syed are corresponding authors, joined by Dr Ikechukwu Achilonu from the University of the Witwatersrand, Professor José Martínez-Oyanedel from the Universidad de Concepción in Chile, and Dr Wanping Chen from 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.

https://www.nature.com/articles/s41598-020-77233-5

Caption

Prof  Syed Khajamohiddin, the UNIZULU researcher  who is one of the researchers who discovered three new classes of detoxification proteins.