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Drug resistance in Plasmodium

Haldar, Kasturi ; Bhattacharjee, Souvik ; Safeukui, Innocent

Nature reviews. Microbiology, 2018-03, Vol.16 (3), p.156-170 [Periódico revisado por pares]

England: Nature Publishing Group

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  • Título:
    Drug resistance in Plasmodium
  • Autor: Haldar, Kasturi ; Bhattacharjee, Souvik ; Safeukui, Innocent
  • Assuntos: 1-Phosphatidylinositol 3-kinase ; Analysis ; Artemisinin ; Chemotherapy ; Cullin ; Drug development ; Drug resistance ; Drug therapy ; Drugs ; Erythrocytes ; Kinases ; Malaria ; Markers ; Mutation ; Parasite resistance ; Parasites ; Plasmodium falciparum ; Populations ; Protein folding ; Substrates ; Ubiquitin-protein ligase ; Vector-borne diseases
  • É parte de: Nature reviews. Microbiology, 2018-03, Vol.16 (3), p.156-170
  • Notas: ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-3
    content type line 23
    ObjectType-Review-1
    K.H., S.B. and I.S. researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and edited the manuscript before submission.
    Author contributions
  • Descrição: A marked decrease in malaria-related deaths worldwide has been attributed to the administration of effective antimalarials against Plasmodium falciparum, in particular, artemisinin-based combination therapies (ACTs). Increasingly, ACTs are also used to treat Plasmodium vivax, the second major human malaria parasite. However, resistance to frontline artemisinins and partner drugs is now causing the failure of P. falciparum ACTs in southeast Asia. In this Review, we discuss our current knowledge of markers and mechanisms of resistance to artemisinins and ACTs. In particular, we describe the identification of mutations in the propeller domains of Kelch 13 as the primary marker for artemisinin resistance in P. falciparum and explore two major mechanisms of resistance that have been independently proposed: the activation of the unfolded protein response and proteostatic dysregulation of parasite phosphatidylinositol 3- kinase. We emphasize the continuing challenges and the imminent need to understand mechanisms of resistance to improve parasite detection strategies, develop new combinations to eliminate resistant parasites and prevent their global spread.
  • Editor: England: Nature Publishing Group
  • Idioma: Inglês
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