%0 Journal Article %T Heterogeneity of molecular resistance patterns in antimony-resistant field isolates of leishmania species from the Western mediterranean area. %+ Aix Marseille Université (AMU) %+ Laboratoire de Parasitologie Médicale, Biotechnologies et Biomolécules (LR11IPT06) %+ Institut Pasteur d'Algérie %+ Université des Sciences et de la Technologie Houari Boumediene = University of Sciences and Technology Houari Boumediene [Alger] (USTHB) %+ Centre méditerranéen de médecine moléculaire (C3M) %+ Service de Parasitologie-Mycologie %+ Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC) %+ Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) %A Jeddi, Fakhri %A Mary, Charles %A Aoun, Karim %A Harrat, Zoubir %A Bouratbine, Aïda %A Faraut, Françoise %A Benikhlef, Rezika %A Pomares, Christelle %A Pratlong, Francine %A Marty, Pierre %A Piarroux, Renaud %< avec comité de lecture %@ 0066-4804 %J Antimicrobial Agents and Chemotherapy %I American Society for Microbiology %V 58 %N 8 %P 4866-74 %8 2014-08 %D 2014 %R 10.1128/AAC.02521-13 %M 24913173 %Z Life Sciences [q-bio] %Z Life Sciences [q-bio]/Microbiology and Parasitology %Z Life Sciences [q-bio]/Microbiology and Parasitology/ParasitologyJournal articles %X Antimonials remain the first-line treatment for the various manifestations of leishmaniasis in most areas where the disease is endemic, and increasing cases of therapeutic failure associated with parasite resistance have been reported. In this study, we assessed the molecular status of 47 clinical isolates of Leishmania causing visceral and cutaneous leishmaniasis from Algeria, Tunisia, and southern France. In total, we examined 14 genes that have been shown to exhibit significant variations in DNA amplification, mRNA levels, or protein expression with respect to resistance to antimonials. The gene status of each clinical isolate was assessed via qPCR and qRT-PCR. We then compared the molecular pattern against the phenotype determined via an in vitro sensitivity test of the clinical isolates against meglumine antimoniate, which is considered the reference technique. Our results demonstrate significant DNA amplification and/or RNA overexpression in 56% of the clinical isolates with the resistant phenotype. All clinical isolates that exhibited significant overexpression of at least 2 genes displayed a resistant phenotype. Among the 14 genes investigated, 10 genes displayed either significant amplification or overexpression in at least 1 clinical isolate; these genes are involved in several metabolic pathways. Moreover, various gene associations were observed depending on the clinical isolates, supporting the multifactorial nature of Leishmania resistance. Molecular resistance features were found in the 3 Leishmania species investigated (Leishmania infantum, Leishmania major, and Leishmania killicki). To our knowledge, this is the first report of the involvement of molecular resistance genes in field isolates of Leishmania major and Leishmania killicki with the resistance phenotype. %G English %L pasteur-01060243 %U https://riip.hal.science/pasteur-01060243 %~ UNICE %~ RIIP %~ CNRS %~ UNIV-AMU %~ RIIP_TUNIS %~ RIIP_ALGERIE %~ AGROPOLIS %~ B3ESTE %~ UNIV-MONTPELLIER %~ UNIV-COTEDAZUR %~ C3M %~ UM-2015-2021