ABSTRACT
In order to define the protein expressional changes related to the process of meglumine antimoniate resistance in anthroponotic cutaneous leishmaniasis [CL], we performed a comparative proteomics analysis on sensitive and resistant strains of Leishmania tropica isolated from Iranian CL patients. Cell proteins were analysed with 2-dimensional electrophoresis and differentially expressed proteins were identified by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor [LACK], alpha tubulin [X2], prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. The study shows the usefulness of proteomics in identifying proteins that may express differences between sensitive and resistant L. tropica isolates
Subject(s)
Humans , Proteomics , Meglumine , Organometallic Compounds , Leishmaniasis, Cutaneous , Electrophoresis, Gel, Two-Dimensional , Mass SpectrometryABSTRACT
Glucantime[R] is the first- line drug for the treatment of all forms of leishmaniasis. Unfortunately, the prevalence of parasites becoming resistant to Glucantime[R] is increasing in several parts of the world including Iran. As protein is the most important target for drugs in response to a variety of signals including drugs so, it seems expression protein patterns in sensitive and resistant Leishmania parasites could greatly help us about the mechanisms of responses to antileishmanial drugs. In this study, we used 2-dimentional gel electrophoresis [2-DE] method to determine protein expression profiles between drug [Glucantime[R]] sensitive and resistant Leishmania tropica isolated from Iranian an throponotic cutaneous leishmaniasis [ACL] patients. We used from the two confirmed genetically of Glucantime[R] sensitive [Mash-4] and resistant [Mash-927] field strains of L. tropica, isolated from ACL patients in north eastern Iran. The two Leishmania isolates were cultured, promastigotes were harvested followed by protein extraction using TCA/Aceton to study protein profiling, 2-DE was done and gels stained with silver nitrate. At least 2236 distinct protein spots were detected. Twelve spots out of them, showed significant changes in expression in resistant compared to sensitive isolates. Of these, 11 protein spots were up- and one was down-regulated. This preliminary study has showed that a number of proteins differentially expressed in drug [Glucan-time [R]] resistance L. tropica and probably the role of these proteins are increasing the parasite resistance against the drug and delay in cell death