Exposure of Plasmodium sporozoites to the intracellular concentration of potassium enhances infectivity and reduces cell passage activity.
Malaria sporozoites migrate through several cells prior to a productive invasion that involves the formation of a parasitophorous vacuole (PV) where sporozoites undergo transformation into Exo-erythorcytic forms (EEFs). The precise mechanism leading to sporozoite activation for invasion is unknown, but prior traversal of host cells is required. During cell migration sporozoites are exposed to large shifts in K(+) concentration. We report here that incubation of sporozoites to the intracellular K(+) concentration enhances 8-10 times the infectivity of Plasmodium berghei and 4-5 times the infectivity of Plasmodium yoelli sporozoites for a hepatocyte cell line, while simultaneously decreasing cell passage activity. The K(+) enhancing effect was time and concentration dependent, and was significantly decreased by K(+) channel inhibitors. Potassium-treated P. berghei sporozoites also showed enhanced numbers of EEFs in non-permissive cell lines. Treated sporozoites had reduced infectivity for mice, but infectivity was enhanced upon Kupffer cell depletion. Transcriptional analysis of K(+) treated and control sporozoites revealed a high degree of correlation in their levels of gene expression, indicating that the observed phenotypic changes are not due to radical changes in gene transcription. Only seven genes were upregulated by more than two-fold in K(+) treated sporozoites. The highest level was noted in PP2C, a phosphatase known to dephosphorylate the AKT potassium channel in plants.
Kumar
Kota Arun
KA
Michael Heidelberger Division of Immunology, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. arun.kumar@med.nyu.edu
Garcia
Celia R S
CR
Chandran
Vandana R
VR
Van Rooijen
N
N
Zhou
Yingyao
Y
Winzeler
Elizabeth
E
Nussenzweig
Victor
V
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D022781:Hepatocytes / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D007728:Kupffer Cells / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D010967:Plasmodium yoelii / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D011188:Potassium / Q000494:pharmacology*; D012692:Serial Passage; D034101:Sporozoites / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology
D011188:Potassium