Comparative proteomics study on meglumine antimoniate sensitive and resistant Leishmania tropica isolated from Iranian anthroponotic cutaneous leishmaniasis patients

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 (×2), 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. RÉSUMÉ Afin de déterminer les modifications de l'expression des protéines liées au processus de résistance à l'antimoniate de méglumine dans la leishmaniose cutanée anthroponotique, nous avons réalisé une analyse protéomique comparative de souches sensibles et de souches résistantes de Leishmania tropica isolées à partir d'échantillons prélevés chez des patients iraniens atteints de la maladie. Les protéines cellulaires ont été analysées par électrophorèse bidimensionnelle ; des protéines différentiellement exprimées ont été identifiées par spectrométrie de masse à temps de vol avec désorption-ionisation laser assistée par matrice. L'analyse d'image des cartes appariées a permis d'identifier sept protéines qui étaient soit surexprimées, soit sous-exprimées : le récepteur de la protéine kinase C activée, la tubuline alpha (×2), la prostaglandine F2-alpha synthase, la protéine disulfide isomérase, une protéine du transport vésiculaire et une protéine hypothétique. L'étude souligne l'utilité de la protéomique dans l'identification des protéines pouvant être différentiellement exprimées selon le caractère sensible ou résistant des souches L. tropica.

Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates

“…Several techniques such as RT-PCR, microarrays, and proteomics are currently used to explore molecular markers of antimony resistance [14,15]. cDNA-amplified fragment length polymorphism (cDNA-AFLP) is one of the most sensitive technologies for detection of differentially expressed gene which does not require any prior information of gene sequences [16, 17].…”

Comparative Two-dimensional Gel Electrophoresis Maps for Amastigote-like Proteomes of Iranian Leishmania Tropica and Leishmania major Isolates

“…On the other hand, the 2-DE method was applied for the detection of proteins that respond to drug resistance during leishmaniasis treatment [21]. The molecular weights of all detected proteins were 14.4 to 116 kDa which is close to Zarean and his colleagues study that they reported most of these proteins to have significant roles in transferring other proteins, heat shock proteins, skeletal proteins, and hypothetical proteins, specifically they have protective roles for DNA structure GMJ.2019;8:e1520 www.gmj.ir and normal metabolism in the cells [21,23,24]. Among the expressed proteins, specific proteins of each isolate may be secreted to patients' skin, which can be introduced as responsible protein/s for the clinical phenomenon of disease.…”

Expression analysis of activated protein kinase C gene (LACK1) in antimony sensitive and resistant Leishmania tropica clinical isolates using real‐time RT‐PCR

“…in 2012, proteomics technique was used to evaluate protein changes in resistant and sensitive isolates of L. tropica . The results determined an increase in the expression level of activated protein kinase C receptor (LACK) . Therefore according to the difference of the LACK protein expression in resistant and sensitive isolates, this gene was suggested to be one of the most probable factors involved in drug resistance.…”

“…Following a proteomics study on L. tropica clinical isolates, which were sensitive and resistant to Glucantime treatment, a number of proteins with different expressions were identified by the mass spectrometry method . Among them, due to the importance of its physiological performance, the activated protein kinase C receptor (LACK) ( Leishmania analogue of the receptors of activated C kinase) antigen was selected, and its expression was investigated in RNA levels in L. tropica clinical isolates that were sensitive and resistant to Glucantime treatment.…”