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These haplotypes have encountered drug pressure and within\u2010host competition with wild\u2010type drug\u2010sensitive parasites. To examine these selective forces in vitro<\/jats:italic>, we genetically engineered P<\/jats:italic><\/jats:styled-content>.\u2009falciparum<\/jats:italic> to express geographically diverse PfCRT<\/jats:styled-content> haplotypes. Variant alleles from the P<\/jats:styled-content>hilippines (PH1<\/jats:styled-content> and PH2<\/jats:styled-content>, which differ solely by the C72S<\/jats:styled-content> mutation) both conferred a moderate gain of chloroquine resistance and a reduction in growth rates in vitro<\/jats:italic>. Of the two, PH2<\/jats:styled-content> showed higher IC<\/jats:styled-content>50<\/jats:sub> values, contrasting with reduced growth. Furthermore, a highly mutated pfcrt<\/jats:italic> allele from C<\/jats:styled-content>ambodia (C<\/jats:styled-content>am734) conferred moderate chloroquine resistance and enhanced growth rates, when tested against wild\u2010type pfcrt<\/jats:italic> in co\u2010culture competition assays. These three alleles mediated cross\u2010resistance to amodiaquine, an antimalarial drug widely used in A<\/jats:styled-content>frica. Each allele, along with the globally prevalent Dd2<\/jats:styled-content> and 7G8<\/jats:styled-content> alleles, rendered parasites more susceptible to lumefantrine, the partner drug used in the leading first\u2010line artemisinin\u2010based combination therapy. These data reveal ongoing region\u2010specific evolution of PfCRT<\/jats:styled-content> that impacts drug susceptibility and relative fitness in settings of mixed infections, and raise important considerations about optimal agents to treat chloroquine\u2010resistant malaria.<\/jats:p>","DOI":"10.1111\/mmi.13035","type":"journal-article","created":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T09:55:53Z","timestamp":1429610153000},"page":"381-395","source":"Crossref","is-referenced-by-count":54,"title":["Balancing drug resistance and growth rates via compensatory mutations in the P<\/i><\/scp>lasmodium falciparum<\/i> chloroquine resistance transporter"],"prefix":"10.1111","volume":"97","author":[{"given":"Ines","family":"Petersen","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Columbia University Medical Center New York NY 10032 USA"},{"name":"Hygiene Institut Abteilung Parasitologie Universit\u00e4tsklinikum Heidelberg 69120 Heidelberg 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