PHARMACOLOGY Correction for “(+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium,” by María Belén Jiménez-Díaz, Daniel Ebert, Yandira Salinas, Anupam Pradhan, Adele M. Lehane, Marie-Eve Myrand-Lapierre, Kathleen G. O’Loughlin, David M. Shackleford, Mariana Justino de Almeida, Angela K. Carrillo, Julie A. Clark, Adelaide S. M. Dennis, Jonathon Diep, Xiaoyan Deng, Sandra Duffy, Aaron N. Endsley, Greg Fedewa, W. Armand Guiguemde, María G. Gómez, Gloria Holbrook, Jeremy Horst, Charles C. Kim, Jian Liu, Marcus C. S. Lee, Amy Matheny, María Santos Martínez, Gregory Miller, Ane Rodríguez-Alejandre, Laura Sanz, Martina Sigal, Natalie J. Spillman, Philip D. Stein, Zheng Wang, Fangyi Zhu, David Waterson, Spencer Knapp, Anang Shelat, Vicky M. Avery, David A. Fidock, Francisco-Javier Gamo, Susan A. Charman, Jon C. Mirsalis, Hongshen Ma, Santiago Ferrer, Kiaran Kirk, Iñigo Angulo-Barturen, Dennis E. Kyle, Joseph L. DeRisi, David M. Floyd, and R. Kiplin Guy, which appeared in issue 50, December 16, 2014, of Proc Natl Acad Sci USA (111:E5455–E5462; first published December 1, 2014; 10.1073/pnas.1414221111).
The authors note that Fig. 5 appeared incorrectly. The corrected figure and its legend appear below.
Fig. 5.
Induction of eryptosis by SJ733 triggers rapid clearance in vivo. When (+)-SJ733 is added to erythrocytes infected with Plasmodium spp., it prevents the action of the putative Na+ ATPase PfATP4 and causes a significant increase in cytosolic Na+ within the parasite, reaching maximal effect within 90 min after treatment. This process results in the immediate arrest of parasite motility and blockade of intracellular parasite replication that reaches maximal potency after 24 h of exposure. Simultaneously, infected, treated erythrocytes begin to enter eryptosis, as characterized by their shrinking and becoming more spherical, becoming significantly more rigid, and exposing PS on their plasma membrane. These effects maximize by 7 h after treatment. In vitro, the drug effects lead to complete arrest of replication within 24 h of treatment, followed by slow death, which is maximal by 96 h. In stark contrast to the in vitro setting, the induction of eryptosis leads to rapid clearance of the infected, treated erythrocytes in vivo.