Nature Communications (Sep 2022)
A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin
- Deyun Qiu,
- Jinxin V. Pei,
- James E. O. Rosling,
- Vandana Thathy,
- Dongdi Li,
- Yi Xue,
- John D. Tanner,
- Jocelyn Sietsma Penington,
- Yi Tong Vincent Aw,
- Jessica Yi Han Aw,
- Guoyue Xu,
- Abhai K. Tripathi,
- Nina F. Gnadig,
- Tomas Yeo,
- Kate J. Fairhurst,
- Barbara H. Stokes,
- James M. Murithi,
- Krittikorn Kümpornsin,
- Heath Hasemer,
- Adelaide S. M. Dennis,
- Melanie C. Ridgway,
- Esther K. Schmitt,
- Judith Straimer,
- Anthony T. Papenfuss,
- Marcus C. S. Lee,
- Ben Corry,
- Photini Sinnis,
- David A. Fidock,
- Giel G. van Dooren,
- Kiaran Kirk,
- Adele M. Lehane
Affiliations
- Deyun Qiu
- Research School of Biology, Australian National University
- Jinxin V. Pei
- Research School of Biology, Australian National University
- James E. O. Rosling
- Research School of Biology, Australian National University
- Vandana Thathy
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Dongdi Li
- Research School of Biology, Australian National University
- Yi Xue
- Research School of Biology, Australian National University
- John D. Tanner
- Research School of Biology, Australian National University
- Jocelyn Sietsma Penington
- Bioinformatic Division, The Walter & Eliza Hall Institute of Medical Research
- Yi Tong Vincent Aw
- Research School of Biology, Australian National University
- Jessica Yi Han Aw
- Research School of Biology, Australian National University
- Guoyue Xu
- Department of Molecular Microbiology & Immunology and Johns Hopkins Malaria Institute, Johns Hopkins School of Public Health
- Abhai K. Tripathi
- Department of Molecular Microbiology & Immunology and Johns Hopkins Malaria Institute, Johns Hopkins School of Public Health
- Nina F. Gnadig
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Tomas Yeo
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Kate J. Fairhurst
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Barbara H. Stokes
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- James M. Murithi
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Krittikorn Kümpornsin
- Wellcome Sanger Institute, Wellcome Genome Campus
- Heath Hasemer
- Research School of Biology, Australian National University
- Adelaide S. M. Dennis
- Research School of Biology, Australian National University
- Melanie C. Ridgway
- Research School of Biology, Australian National University
- Esther K. Schmitt
- Novartis Pharma AG, Novartis Campus
- Judith Straimer
- Novartis Institute for Tropical Diseases
- Anthony T. Papenfuss
- Bioinformatic Division, The Walter & Eliza Hall Institute of Medical Research
- Marcus C. S. Lee
- Wellcome Sanger Institute, Wellcome Genome Campus
- Ben Corry
- Research School of Biology, Australian National University
- Photini Sinnis
- Department of Molecular Microbiology & Immunology and Johns Hopkins Malaria Institute, Johns Hopkins School of Public Health
- David A. Fidock
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Giel G. van Dooren
- Research School of Biology, Australian National University
- Kiaran Kirk
- Research School of Biology, Australian National University
- Adele M. Lehane
- Research School of Biology, Australian National University
- DOI
- https://doi.org/10.1038/s41467-022-33403-9
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 18
Abstract
In a recent clinical trial for oral administration of cipargamin in individuals with malaria, there was an emergence of recrudescent parasites with a G358S mutation in PfATP4. In this work, the authors investigate the effect of this mutation on the function of the ATPase, on parasite growth and susceptibility to antimalarial drugs.
