@article{1198ec186c364ab6a56197201e6f8a5e,
title = "Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine",
abstract = "The lack of a long-term in vitro culture method has severely restricted the study of Plasmodium vivax, in part because it limits genetic manipulation and reverse genetics. We used the recently optimized Plasmodium cynomolgi Berok in vitro culture model to investigate the putative P. vivax drug resistance marker MDR1 Y976F. Introduction of this mutation using clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) increased sensitivity to mefloquine, but had no significant effect on sensitivity to chloroquine, amodiaquine, piperaquine, and artesunate. To our knowledge, this is the first reported use of CRISPR-Cas9 in P. cynomolgi, and the first reported integrative genetic manipulation of this species.",
keywords = "Plasmodium cynomolgi, Plasmodium vivax, antimalarial drug resistance, chloroquine, CRISPR-Cas9, mefloquine, molecular markers",
author = "Ward, {Kurt E.} and Peter Christensen and Annie Racklyeft and Dhingra, {Satish K.} and Chua, {Adeline C. Y.} and Caroline Remmert and Rossarin Suwanarusk and Jessica Matheson and Blackman, {Michael J.} and Osamu Kaneko and Kyle, {Dennis E.} and Lee, {Marcus C. S.} and Moon, {Robert W.} and Georges Snounou and Laurent R{\'e}nia and Fidock, {David A.} and Bruce Russell and Pablo Bifani",
note = "Funding Information: This work was supported by the Agency for Science, Technology, and Research, Singapore (A*STAR) (core funding to A*STAR Infectious Diseases Laboratory, and grant number JCO-DP BMSI/15-800006-SIGN to L. R.); Health Research Council, New Zealand (grant number 17/ 678 e-ASIA Research Program to B. R.); University of Otago (Deans Bequest Grant to B. R.); Japanese Society for the Promotion of Science (Invitational Fellowship for Research in Japan to B. R.); US National Institutes of Health (grant number R01 AI050234 to D. A. F.); Agence Nationale de la Recherche, France (grant number ANR-17-CE13-0025-01 to G. S.); Francis Crick Institute (support to M. J. B.), which receives its core funding from Cancer Research UK (grant number FC001043), UK Medical Research Council (MRC) (grant number FC001043), and Wellcome (grant number FC001043); Wellcome (grant number 206194/Z/17/Z to M. C. S. L.); MRC and UK Department for International Development (grant number MR/M021157/1 MRC Career Development Award to R. W. M.); and Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (grant number 22K19441 Grants-in-Aid for Scientific Research to O. K.). Funding to pay the Open Access publication charges for this article was provided by CAUL – Council of Australian University Librarians. Copyright: {\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.",
year = "2023",
month = may,
day = "15",
doi = "10.1093/infdis/jiac469",
language = "English",
volume = "227",
pages = "1121--1126",
journal = "The Journal of infectious diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "10",
}