A proteomic analysis of arsenical drug resistance in Trypanosoma brucei

Foucher, A.L., McIntosh, A., Douce, G. , Wastling, J., Tait, A. and Turner, C.M.R. (2006) A proteomic analysis of arsenical drug resistance in Trypanosoma brucei. Proteomics, 6(9), pp. 2726-2732. (doi: 10.1002/pmic.200500419)

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Publisher's URL: http://dx.doi.org/10.1002/pmic.200500419

Abstract

We have undertaken 2-DE and MS to identify proteins associated with arsenical drug resistance in Trypanosoma brucei. This parasite causes sleeping sickness in humans, and arsenical drug resistance is a significant potential problem. Comparative analysis of approximately 2000 spots resolved by 2-DE in the soluble proteomes of drug-sensitive and drug-resistant isogenic lines of T. brucei identified a protein spot whose absence associated with resistance to the arsenical drug, Cymelarsan. MS matched this protein to an identical pair of tandem genes Tb09.211.0120 and 0130 that encode a putative nascent polypeptide associated complex subunit. This protein also occurs as an isoform located in both resistant and sensitive lines at a similar molecular weight, but different pI. The difference between isogenic lines was confirmed by Western blot using an antibody against recombinant protein. Both genes were identical in sequence between drug-sensitive and drug-resistant lines and both were transcribed as determined by RT-PCR. We postulate that the missing protein isoform arose due to the lack of a PTM.

Item Type:Articles
Keywords:Cymelarsan, Drug resistance, Parasite, Proteome, Trypanosoma brucei
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McIntosh, Ms Anne and Douce, Dr Gillian
Authors: Foucher, A.L., McIntosh, A., Douce, G., Wastling, J., Tait, A., and Turner, C.M.R.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proteomics
ISSN:1615-9853

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