title: Tricks in Plasmodium's molecular repertoire--escaping 3'UTR excision-based conditional silencing of the chloroquine resistance transporter gene.
abstract: In the human malaria parasite Plasmodium falciparum, the major determinant of chloroquine resistance, P. falciparum chloroquine resistance transporter (pfcrt), likely plays an essential role in asexual blood stages, thus precluding conventional gene targeting approaches. We attempted to conditionally silence the expression of its ortholog in Plasmodium berghei (pbcrt) through Flp recombinase-mediated excision of the 3'untranslated region (UTR) during mosquito passage. However, parasites maintained pbcrt expression despite 3'UTR excision. Characterisation of these pbcrt mRNAs, by 3'rapid amplification of cDNA ends, identified several replacement 3'UTR sequences. Our observations demonstrate the astounding genetic plasticity of this parasite when faced with the loss of an essential gene.
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ecker
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Lewis
authors.forename: Eric H
authors.initials: EH
authors.lastname: Ekland
authors.forename: Bamini
authors.initials: B
authors.lastname: Jayabalasingham
authors.forename: David A
authors.initials: DA
authors.lastname: Fidock
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D009033:Culicidae; D004351:Drug Resistance; D020868:Gene Silencing; D008288:Malaria / Q000469:parasitology / Q000635:transmission; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D015800:Protozoan Proteins; D002738:Chloroquine