Instability of aquaglyceroporin (AQP) 2 contributes to drug resistance inTrypanosoma brucei

0540068 - BC 2021 RIV US eng J - Článek v odborném periodiku
Quintana, J.F. - Bueren-Calabuig, J. - Zuccotto, F. - de Koning, H.P. - Horn, D. - Field, Mark Christian
Instability of aquaglyceroporin (AQP) 2 contributes to drug resistance inTrypanosoma brucei.
PLoS Neglected Tropical Diseases. Roč. 14, č. 7 (2020), č. článku e0008458. ISSN 1935-2735. E-ISSN 1935-2735
GRANT EU: Wellcome Trust(GB) 204697/Z/16/Z
Grant ostatní: Medical Research Council(GB) MR/ P009018/1
Institucionální podpora: RVO:60077344
Klíčová slova: human african trypanosomiasis * cross-resistance * surface-proteins * pentamidine * phosphorylation * aquaporin-2 * glycosylation * melarsoprol * expression * oligomerization
Obor OECD: Tropical medicine
Impakt faktor: 4.411, rok: 2020
Způsob publikování: Open access
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008458

Author summary Understanding mechanisms that make cells sensitive to xenobiotics (including drugs) is of great importance to both drug development and public health. For the latter, emergence of resistance is particularly important to monitor as well as to predict. Trypanosomes are a major global health burden and for several drugs resistance has emerged and is a considerable concern. Here we have examined the sensitivity to pentamidine, which is mainly mediated by an aquaglyceroporin, a surface channel. We find that the protein is highly sensitive to mutation, rendering the protein unstable, and rendering parasites resistant to pentamidine. As this also includes mutant forms recovered from patients where pentamidine treatment has failed, we suggest that the instability of aquaglyceroporin is an important contributor towards treatment failure.
Trvalý link: http://hdl.handle.net/11104/0317736