title: [Differential expression of proteins in Leishmania (Viannia) panamensis associated with mechanisms of resistance to meglumine antimoniate].
abstract: BACKGROUND
  The well-known drug resistance mechanisms to pentavalent antimony have been widely described in strains of the Leishmania subgenus, but little is known about the mechanisms of resistance and the proteins associated with it in strains of the Viannia subgenus such as Leishmania panamensis.
  
  
  OBJECTIVE
  Differentially expressed proteins were identified between pentavalent antimonial sensitive and resistant L. panamensis (UA140) strains, and the role of these proteins was analyzed as possible resistance mechanisms.
  
  
  METHODS
  The protein lysates of pentavalent antimony sensitive and resistant strains were separated by two-dimensional gel electrophoresis,and the protein patterns compared. The proteins identified as overexpressed were separated and analyzed using MALDI-TOF/TOF (Matrix Assisted Laser Desorption Ionization/Time of Flight). The level of mRNA expression of five of these proteins was quantified using real-time PCR.
  
  
  RESULTS
  On the 2-dimensional gels, 532 ± 39 protein spots were identified for the sensitive strains, and 541 ± 43 spots for the resistant strains. Ten spots were overexpressed in the resistant strain and identified as heat shock protein (Hsp60 mitochondrial, Hsp70 cytosolic and mitochondrial), disulfide isomerase, cysteine protease, enolase, elongation factor 5-alpha, the proteasome alpha-5 subunit and two hypothetical proteins named as Sp(2) and Sp(25).
  
  
  CONCLUSIONS
  This is the first proteomic study conducted with a L. panamensis resistant strain where several proteins were identified and related with the parasite resistance mechanism to pentavalent antimony. This opens the way for future studies aimed at modulating the drug resistance or at evaluating these proteins as therapeutic targets.
authors.affiliation: Programa de Estudio y Control de Enfermedades Tropicales, PECET, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Ronald Guillermo
authors.initials: RG
authors.lastname: Peláez
authors.forename: Carlos Enrique
authors.initials: CE
authors.lastname: Muskus
authors.forename: Patricia
authors.initials: P
authors.lastname: Cuervo
authors.forename: Marcel
authors.initials: M
authors.lastname: Marín-Villa
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004351:Drug Resistance; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D018334:Leishmania guyanensis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008536:Meglumine / Q000494:pharmacology*; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000494:pharmacology*; D040901:Proteomics; D015800:Protozoan Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D016053:RNA, Protozoan / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013382:Subtraction Technique
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D008536:Meglumine; D000077485:Meglumine Antimoniate