Identification of CβS and ODC antimony resistance markers in anthroponotic cutaneous leishmaniasis field isolates by gene expression profiling

Antiparasitic resistance represents a serious global public health concern with tremendous economic and safety implications. This study intended to investigate the expression of the two major resistant markers: cystathionine β synthase (CβS) and ornithine decarboxylase (ODC) in antimony unresponsive Leishmania tropica isolates compared to responsive ones. Twenty-six patients were randomly selected from widely known foci of anthroponotic cutaneous leishmaniasis in southeastern Iran. Written informed consent of the patients was obtained. Two smears were prepared from the edge of each active lesion; one for microscopic direct smear preparation and the other for inoculation into monophasic NNN media, then for mass production of promastigotes into RPMI-1640 monophasic culture for performing nested PCR and gene expression quantification by real-time PCR. Twenty-six patients consisting of 13 unresponsive and 13 responsive equally distributed among female and male groups. All cases were identified to be L. tropica. Both resistant gene markers were significantly up-regulated in unresponsive and responsive isolates. The findings showed that CβS and ODC are directly linked with the resistance to L. tropica. Alternative drugs or combination therapy and monitoring drug resistance to prevent the spread of resistant isolates are proper strategies to control the disease.