{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:09:31Z","timestamp":1791234571141,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n 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\n Leishmania<\/jats:named-content>\n 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\n in vitro<\/jats:italic>\n 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\n Leishmania<\/jats:named-content>\n resistance. Molecular resistance features were found in the 3\n Leishmania<\/jats:named-content>\n species investigated (\n Leishmania infantum<\/jats:named-content>\n ,\n Leishmania major<\/jats:named-content>\n , and\n Leishmania killicki<\/jats:named-content>\n ). To our knowledge, this is the first report of the involvement of molecular resistance genes in field isolates of\n Leishmania major<\/jats:named-content>\n and\n Leishmania killicki<\/jats:named-content>\n with the resistance phenotype.\n <\/jats:p>","DOI":"10.1128\/aac.02521-13","type":"journal-article","created":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T03:42:17Z","timestamp":1402371737000},"page":"4866-4874","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Heterogeneity of Molecular Resistance Patterns in Antimony-Resistant Field Isolates of Leishmania Species from the Western Mediterranean Area"],"prefix":"10.1128","volume":"58","author":[{"given":"Fakhri","family":"Jeddi","sequence":"first","affiliation":[{"name":"Laboratoire de Parasitologie-Mycologie, CHU Timone, UMR MD3 Aix-Marseille Universit\u00e9, Marseille, 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