Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

<jats:title>ABSTRACT</jats:title><jats:p><jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Plasmodium falciparum</jats:named-content>has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Apicomplexa</jats:named-content>parasites.<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>genome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters:<jats:italic>Pfmrp1</jats:italic>, previously associated with decreased parasite drug susceptibility, and the poorly studied<jats:italic>Pfmrp2</jats:italic>. The role of<jats:italic>Pfmrp2</jats:italic>polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of the<jats:italic>Pfmrp2</jats:italic>genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found that<jats:italic>Pfmrp2</jats:italic>harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identified<jats:italic>Pfmrp2</jats:italic>polymorphisms with altered<jats:italic>in vitro</jats:italic>susceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggested<jats:italic>Pfmrp2</jats:italic>polymorphisms modulate the parasite's<jats:italic>in vitro</jats:italic>response to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association with<jats:italic>in vivo</jats:italic>parasite clearance. In conclusion, our study reveals that the<jats:italic>Pfmrp2</jats:italic>gene is the most diverse ABC transporter known in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>with a potential role in antimalarial drug resistance.</jats:p>

Original publication

DOI

10.1128/aac.03337-14

Type

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

12/2014

Volume

58

Pages

7390 - 7397