English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  The prevalence of drug resistance amongst the human malaria  Plasmodium  species has most commonly been associated with genomic mutation within the parasites. This phenomenon necessitates evolutionary predictive studies of possible resistance mutations, which may occur when a new drug is introduced. Therefore, identification of possible new  Plasmodium falciparum  dihydrofolate reductase ( Pf DHFR) mutants that confer resistance to antifolate drugs is essential in the process of antifolate anti-malarial drug development.    Methods  A system to identify mutations in  Pfdhfr  gene that confer antifolate drug resistance using an animal  Plasmodium  parasite model was developed. By using error-prone PCR and  Plasmodium  transfection technologies, libraries of  Pfdhfr  mutant were generated and then episomally transfected to  Plasmodium berghei  parasites, from which pyrimethamine-resistant  Pf DHFR mutants were selected.    Results  The principal mutation found from this experiment was S108N, coincident with the first pyrimethamine-resistance mutation isolated from the field. A transgenic  P. berghei , in which endogenous  Pbdhfr  allele was replaced with the mutant  Pfdhfr S108N  , was generated and confirmed to have normal growth rate comparing to parental non-transgenic parasite and also confer resistance to pyrimethamine.    Conclusion  This study demonstrated the power of the transgenic  P. berghei  system to predict drug-resistant  Pfdhfr  mutations in an  in vivo  parasite/host setting. The system could be utilized for identification of possible novel drug-resistant mutants that could arise against new antifolate compounds and for prediction the evolution of resistance mutations.

Selection of drug resistant mutants from random library of Plasmodium falciparum dihydrofolate reductase in Plasmodium berghei model