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Journal of Ecosystem & Ecography | ISSN: 2157-7625 | Volume: 8
June 28-29, 2018 | Alexandria, Egypt
International Pre Conference Workshop on
Microbial Ecology & Eco Systems
Introduction of tryptophan residues towards the cytoplasmic end of the Trepanosoma brucei
Aquaporin
1Ali E Alghamdi, 2 Mohamed E. Wagih and 1Harry P. de Koning
1Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom
2Canadian Academy of Sciences, Canada
African Trepanosoma brucei cause sleeping sickness in humans, a disease that is typically fatal without chemotherapy.
Unfortunately, drug resistance is common and our understanding of the underlying mechanisms remains incomplete. In
Trypanosoma, three aquaporins genes, AQP1-3, have been identified. Recent studies have shown that loss of AQP2, a channel
with an unusual selectivity filter, is specifically responsible for MPXR, leading to the hypothesis that some of the clinical
trypanocides, specifically pentamidine and the melaminophenyl arsenicals enter through these aquaporins. In T. brucei, the
TbAQP2 protein was found to be a highly efficient transporter for pentamidine and melarsoprol and introduction of the
corresponding gene into Leishmania mexicana made these parasites more than 1000-fold more sensitive to melarsoprol, and
40-fold more sensitive to pentamidine. Therefore, an understanding of the mechanisms of AQP2-mediated drug uptake in
African trypanosomes will facilitate the advancement of diagnostic tools and perhaps at the same time the improvement of
enhanced treatments. We report here the construction of several genetic mutations (single amino acid substitutions) in AQP2
to investigate their effects on the ability of the gene for drug sensitivity and drug transport. As part of this strategy, leucine
residues were replaced by tryptophan in three suggested sites in the Tb AQP2 gene. The results of introducing tryptophan
residues in L84 and L118 in the TbAQP2 showed some loss of pentamidine susceptibility compared to the wild-type cells,
whereas L218 showed equal sensitivity to pentamidine compared to the wild-type cells.
Keywords: African trypanosomiasis, drug resistance, Leishmania spp, Trepanosoma brucei
Biography
Ali Efan Alghamdi is currently a PhD student of the Genetics of Leishmania at the Institute of Infection, Immunity and Inflammation College of Medical, Veterinary
and Life Sciences, University of Glasgow. He studied his Master degree in Biotechnology from Macquarie University, School of Science in Australia, and his
in the Department of Biology, Albaha University, Albaha, Saudi Arabia.
Ali E. Alghamdi et al., J Ecosys Ecograph 2018, Volume: 8
DOI: 10.4172/2157-7625-C2-036