Proteomic analysis of Trypanosoma cruzi resistance to Benznidazole.
The first proteomic analysis of Trypanosoma cruzi resistance to Benznidazole (BZ) is presented. The differential proteome of T. cruzi with selected in vivo resistance to Benznidazole (BZR and Clone27R), its susceptible pairs (BZS and Clone9S), and a pair from a population with Benznidazole- in vitro-induced resistance (17LER) and the susceptible pair 17WTS were analyzed by two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (MS) for protein identification. Out of 137 spots analyzed through MS, 110 were identified as 56 distinct proteins. Out of the 56 distinct proteins, 36 were present in resistant, 9 in susceptible, and 11 in both phenotypes. Among the proteins identified in resistant samples, 5 were found in Cl 27R and in BZR (calpain-like cysteine peptidase, hypothetical protein conserved 26 kDa, putative peptidase, peroxiredoxin and tyrosine amino transferase) and 4 in Cl 27R and 17LER (cyclophilin A, glutamate dehydrogenase, iron superoxide dismutase and nucleoside diphosphate kinase). As for the proteins identified in Benznidazole-susceptible samples, PGF-2a was found in BZS and 17WTS. A functional category analysis showed that the proteins involved with transcription and protein destination were overexpressed for the Benznidazole-resistant phenotype. Thus, the present study provides large-scale, protein-related information for investigation of the mechanism of T. cruzi resistance to Benznidazole.
Andrade
Hélida M
HM
Laboratório de Parasitologia Celular e Molecular, Centro de Pesquisa René Rachou/FIOCRUZ, Brazil. helidandrade@gmail.com
Murta
Silvane M F
SM
Chapeaurouge
Alex
A
Perales
Jonas
J
Nirdé
Phillipe
P
Romanha
Alvaro J
AJ
D000818:Animals; D021984:Cyclophilin A / Q000032:analysis / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000378:metabolism; D004351:Drug Resistance; D015180:Electrophoresis, Gel, Two-Dimensional; D005969:Glutamate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis / Q000378:metabolism; D009593:Nitroimidazoles / Q000494:pharmacology*; D009701:Nucleoside-Diphosphate Kinase / Q000032:analysis / Q000378:metabolism; D010447:Peptide Hydrolases / Q000032:analysis / Q000378:metabolism; D054464:Peroxiredoxins / Q000032:analysis / Q000378:metabolism; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D015800:Protozoan Proteins / Q000032:analysis / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014344:Trypanocidal Agents / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000032:analysis / Q000378:metabolism
D009593:Nitroimidazoles; D020543:Proteome; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase; D054464:Peroxiredoxins; D013482:Superoxide Dismutase; D005969:Glutamate Dehydrogenase; D014444:Tyrosine Transaminase; D009701:Nucleoside-Diphosphate Kinase; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D021984:Cyclophilin A; C009999:benzonidazole