ABSTRACT
Introduction: Malaria parasites increasingly develop resistance to all drugs available in the market, hampering the goal of reducing malaria burden. Methods: Herein, we evaluated the impact of a single-nucleotide variant, E738K, present in the 26S proteasome regulatory subunit rpn2 gene, identified in Plasmodium chabaudi resistant parasites. Plasmids carrying a functional rpn2 interspecies chimeric gene with 5' recombination region from P. falciparum and 3' from P. chabaudi were constructed and transfected into Dd2 P. falciparum parasites. Results and discussion: The 738K variant parasite line presented increased parasite survival when subjected to dihydroartemisinin (DHA), as well as increased chymotrypsin-like activity and decreased accumulation of polyubiquitinated proteins. We thus conclude that the ubiquitin-proteasome pathway, including the 738K variant, play an important role in parasite response to DHA, being the first report of a mutation in a potential DHA drug target enhancing parasite survival and contributing to a significant advance in the understanding the biology of artemisinin resistance.
Subject(s)
Antimalarials , Artemisinins , Plasmodium falciparum , Antimalarials/pharmacology , Artemisinins/pharmacology , Mutation , Plasmodium falciparum/drug effects , Plasmodium falciparum/genetics , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , Protozoan Proteins/genetics , Protozoan Proteins/metabolismABSTRACT
O objetivo deste estudo é descrever as características clínicas, mamográficas e ultra-sonográficas de três casos de mastite granulomatosa idiopática. Esta afecção pode simular câncer de mama nos exames clínico e mamográfico, porém os achados ultra-sonográficos de múltiplas imagens tubulares hipoecóicas, contíguas e confluentes em mulheres jovens com história de lactação recente sugerem o diagnóstico de mastite granulomatosa idiopática.