Journal article

A single point mutation in the Plasmodium falciparum FtsH1 metalloprotease confers actinonin resistance

Christopher D Goodman, Taher Uddin, Natalie J Spillman, Geoffrey McFadden

eLife | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2020

Abstract

The antibiotic actinonin kills malaria parasites (Plasmodium falciparum) by interfering with apicoplast function. Early evidence suggested that actinonin inhibited prokaryote-like post-translational modification in the apicoplast; mimicking its activity against bacteria. However, Amberg Johnson et al. (2017) identified the metalloprotease TgFtsH1 as the target of actinonin in the related parasite Toxoplasma gondii and implicated P. falciparum FtsH1 as a likely target in malaria parasites. The authors were not, however, able to recover actinonin resistant malaria parasites, leaving the specific target of actinonin uncertain. We generated actinonin resistant P. falciparum by in vitro selection..

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Grants

Awarded by National Health and Medical Research Council


Awarded by Australian Research Council


Funding Acknowledgements

National Health and Medical Research Council Project Grant APP1106213 Christopher D Goodman Geoff McFaddenNational Health and Medical Research Council Project Grant APP1162550 Christopher D Goodman Geoff McFaddenAustralian Research Council Laureate Fellowship FL170100008 Geoff McFaddenNational Health and Medical Research Council CJ Maritn Felowship APP1072217 Natalie Jane SpillmanThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.