Team:BOKU-Vienna/Description
Our Idea:
A Novel Approach in Buruli Ulcer
Diagnostics
Neglected Diseases
and a realistic chance of making a difference
In our search for a meaningful project with the potential of generating a tangible value for society as a whole, we took the approach of looking for challenges and brainstorming solutions. Hence, we pragmatically started to screen for current problems in the sectors of medicine, life sciences, environmental sciences and others. There were plenty of issues which we found compelling and where we thought synthetic biology may make a difference – phage therapy, carbon dioxide and methane fixation, or vitamin production to fight deficiencies. Even though we found promising approaches to all of these issues, and we would have loved to follow suit on all of them, we had to pick one. Our choice fell on the one which appeared the most feasible and pressing at a time: the development of a new diagnostic tool for the treatment of a neglected tropical skin disease. The fact that the WHO has listed the improvement of quick diagnostic tests as a priority in their action plan against neglected tropical skin diseases [1] further encouraged us to follow this direction and soon, a more detailed project plan was drafted.
Buruli Ulcer
the third most common mycobacterial disease
When we started looking into neglected tropical diseases, one of the most pressing issues cited by the WHO was Buruli Ulcer. A hard to detect disease in Africa and some parts of South America. Buruli Ulcer is an infectious disease caused by Mycobacterium ulcerans, and it owes its symptoms to mycolactone [1]. This bacterial metabolite weakens the host immune response which leads to lesions and tissue death in the progression of the disease [1]. Although mortality from Buruli Ulcer is low, many healed patients exhibit lasting deformations not only of the skin, but also of bones [1]. Thus, without question, giving attention to this neglected disease felt worthwhile and meaningful and we were motivated to start researching and brainstorming solutions.
The criticality
of early-stage selective diagnosis for directed treatment
Diving into more and more details about Buruli Ulcer, the necessity of reliable, cheap and easy detection methods crystallized as a major priority in scientific literature and on behalf of the WHO [1]. Most importantly, early treatment with targeted antibiotics is crucial for complete recovery [1, 6]. Therefore, we further directed our focus on detection methods and developments of tools for diagnosis. While several techniques do exist, many of them require highly trained personnel, well equipped laboratories and time and are overall resource-intensive [1 ,3]. We started to dive deeper in what has already been known about the causative agent and its producer, and studies examining potential novel approaches in the diagnosis.
An improved tool
for Buruli Ulcer diagnosis
The issue proofed to be a real hot potato with several publications on novel approaches. Several approaches exist which rely on the specific detection of mycolactone, the macrolide excreted as the pathogenicity factor of Buruli Ulcer. In fact, this approach has also been suggested by the WHO and previously followed by a group of researchers who exploit that relation in thin layer chromatography [1,8]. The basic principle for the detection of mycolactone has been shown to be an RNA-structure called aptamer, which changes its conformation if mycolactone is present [3,4,5,6]. Our search thus further centered around the specific interactions of mycolactone and the potential of detecting Mycobacterium ulcerans based on the interaction of this toxin with the aptamer. After an extensive literature research and a conversation with Prof. Dr. Kishi about the significance of the new approach, we finalized a draft of our new diagnostic tool.
Links
[1] WHO, 2019: Fact Sheet on Buruli Ulcer.
[2] WHO, 2016: Distribution of Buruli Ulcer worldwide.
[3] Sakyi, .; Aboagye, S.; Otchere, I.D. and Yeboah-Manu, D. (2016). Clinical and Laboratory Diagnosis of Buruli Ulcer Disease: A Systematic Review. Canadian Journal of Infectious Diseases and Medical Microbiology. Vol. 2016.
[4] Sakyi, S.A.; Aboagye, S.Y.; Otchere, I.D.; Liao, A.M.; Caltagirone, T.G. and Yeboah-Manu, D. (2016) RNA Aptamer That Specifically Binds to Mycolactone and Serves as a Diagnostic Tool for Diagnosis of Buruli Ulcer. PLoS Negl Trop Dis. Volume 10(10).
[5] Berens, C.; Groher, F. and Suess, D. (2014). RNA aptamers as genetic control devices: The potential of riboswitches as synthetic elements for regulating gene expression. Biotechnol J. Volume 10(2). doi: 10.1002/biot.201300498
[6] Zhang, J.; Lau, M.W. and Ferré-D’Amaré, A.R. (2010). Ribozymes and Riboswitches: Modulation of RNA function by small molecules. Biochemistry. Volume 49(43). doi: 10.1021/bi1012645.
[7] Tobias, N. J. ; Seemann, T.; Pidot, S. J.; Porter, J. L.; Marsollier, L.; Marion, E. and Stinear, T. P. (2009). Mycolactone gene expression is controlled by strong SigA-like promoters with utility in studies of Mycobacterium ulcerans and buruli ulcer. PLoS neglected tropical diseases. Volume 3(11)
[8] Wadagni, A.M.; Frimpong, D.M.; Phanzu, A.; Ablordey, E.; Kacou, M.; Gbedevi, E.; Marion, E.; Xing, Y.; Babu, V.S.; Phillips, R.O.; Wansbrough-Jones, M.; Kishi, Y. and Asiedu, K. (2015). Simple, Rapid Mycobacterium ulcerans Disease Diagnosis from Clinical Samples by Fluorescence of Mycolactone on Thin Layer Chromatography. PLoS Neglected Tropical Diseases. Volume 9(11). doi:10.1371/journal.pntd.0004247
