Chloroquine Transport via the Malaria Parasite’s Chloroquine Resistance Transporter
Rowena E. Martin,1,*
Rosa V. Marchetti,1
Anna I. Cowan,2
Susan M. Howitt,1
Stefan Bröer,1
Kiaran Kirk1
The emergence and spread of chloroquine-resistant
Plasmodium falciparum malaria parasites has been a disaster for world health.
Resistance is conferred by mutations in the Chloroquine Resistance
Transporter (PfCRT), an integral membrane protein localized
to the parasite’s internal digestive vacuole. These mutations
result in a marked reduction in the accumulation of chloroquine
(CQ) by the parasite. However, the mechanism by which this occurs
is unclear. We expressed both wild-type and resistant forms
of PfCRT at the surface of
Xenopus laevis oocytes. The resistant
form of PfCRT transported CQ, whereas the wild-type protein
did not. CQ transport via the mutant PfCRT was inhibited by
CQ analogs and by the resistance-reverser verapamil. Thus, CQ
resistance is due to direct transport of the drug via mutant
PfCRT.
2 The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 0200, Australia.
* To whom correspondence should be addressed. E-mail: rowena.martin{at}anu.edu.au
