title: Down regulation of KMP-11 in Leishmania infantum axenic antimony resistant amastigotes as revealed by a proteomic screen.
abstract: The therapeutic mainstay against the protozoan parasite Leishmania is still based on the antiquated pentavalent antimonials, but resistance is increasing in several parts of the world. Resistance is now partly understood in laboratory promastigote isolates, but the mechanism leading to drug resistance in amastigote isolates is lagging behind. Here we describe a comparative proteomic analysis of a genetically related pair of antimonial-sensitive and -resistant Leishmania infantum axenic amastigote strains. The proteomics screen has highlighted a number of proteins differentially expressed in the resistant parasite. The expression of the protein argininosuccinate synthetase (ARGG) was increased in the drug resistant mutant while a decrease in the expression of the kinetoplastid membrane protein (KMP-11) correlated with the drug resistance phenotype. This proteomic screen highlighted several novel proteins that are putatively involved in resistance to antimonials.
authors.affiliation: Centre de Recherche en Infectiologie du Centre de Recherche du CHUQ and Division de Microbiologie, Faculté de Médecine, Université Laval, Que., Canada G1V 4G2.
authors.forename: Karima
authors.initials: K
authors.lastname: El Fadili
authors.forename: Jolyne
authors.initials: J
authors.lastname: Drummelsmith
authors.forename: Gaétan
authors.initials: G
authors.lastname: Roy
authors.forename: Armando
authors.initials: A
authors.lastname: Jardim
authors.forename: Marc
authors.initials: M
authors.lastname: Ouellette
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001124:Argininosuccinate Synthase / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D015536:Down-Regulation; D004351:Drug Resistance / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression; D018314:Leishmania infantum / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D016366:Open Reading Frames; D040901:Proteomics / Q000379:methods*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D016053:RNA, Protozoan / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D016053:RNA, Protozoan; C090009:kinetoplastid membrane protein 11, Leishmania donovani; D001124:Argininosuccinate Synthase; D000967:Antimony Sodium Gluconate