The role of PfPanK in the antiplasmodial activity of pantothenate analogues

Description

The malaria-causing blood stage of Plasmodium falciparum requires extracellular
pantothenate for proliferation. The parasite converts pantothenate into coenzyme A
(CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Multiple
antiplasmodial pantothenate analogues, including pantothenol and CJ-15,801, kill the
parasite by targeting CoA biosynthesis/utilisation. Their mechanism of action, however,
remains unknown.
In my talk, I will show that I have generated parasites that are resistant to pantothenol
or CJ-15,801 through step-wise drug pressuring. Whole-genome sequencing revealed
mutations in one of two putative PanK genes in each resistant line that significantly
alter PfPanK activity. The mutants exhibit a different sensitivity profiles to different
antiplasmodial pantothenate analogues, with one mutant line becoming hypersensitive
to some of these compounds. I will then present evidence consistent with the different
pantothenate analogue classes having different mechanisms of action.

Date & time

3–3.30pm 13 October 2017

Location

Slatyer Seminar Room, D.A. Brown Building (Bldg 47), Daley Road, ANU

Speakers

Erick Tjhin Lab - PhD Candidate - Saliba Group

Contacts

 Rowena Martin
 61 (0) 2 6197 0051

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