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,...
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Veröffentlicht in: | Molecular and biochemical parasitology 2007-11, Vol.156 (1), p.32-40 |
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creator | Kumar, Kota Arun Garcia, Celia R.S. Chandran, Vandana R. Van Rooijen, N. Zhou, Yingyao Winzeler, Elizabeth Nussenzweig, Victor |
description | 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. |
doi_str_mv | 10.1016/j.molbiopara.2007.07.004 |
format | Article |
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+ 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.</description><identifier>ISSN: 0166-6851</identifier><identifier>EISSN: 1872-9428</identifier><identifier>DOI: 10.1016/j.molbiopara.2007.07.004</identifier><identifier>PMID: 17714805</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Cell invasion ; Cell Line ; Cercopithecus aethiops ; COS Cells ; Hepatocytes - parasitology ; Host-Parasite Interactions ; Humans ; Kupffer Cells - parasitology ; Mice ; Mice, Inbred C57BL ; Plasmodium ; Plasmodium berghei ; Plasmodium berghei - drug effects ; Plasmodium berghei - growth & development ; Plasmodium berghei - pathogenicity ; Plasmodium yoelii - drug effects ; Plasmodium yoelii - growth & development ; Plasmodium yoelii - pathogenicity ; Potassium - pharmacology ; Potassium shifts ; Serial Passage ; Sporozoites ; Sporozoites - drug effects ; Sporozoites - growth & development ; Sporozoites - physiology</subject><ispartof>Molecular and biochemical parasitology, 2007-11, Vol.156 (1), p.32-40</ispartof><rights>2007 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-345acb6cc67059c1bbca19d5d3fa41742bc38a42734b70316732e686b946de2c3</citedby><cites>FETCH-LOGICAL-c469t-345acb6cc67059c1bbca19d5d3fa41742bc38a42734b70316732e686b946de2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.molbiopara.2007.07.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17714805$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumar, Kota Arun</creatorcontrib><creatorcontrib>Garcia, Celia R.S.</creatorcontrib><creatorcontrib>Chandran, Vandana R.</creatorcontrib><creatorcontrib>Van Rooijen, N.</creatorcontrib><creatorcontrib>Zhou, Yingyao</creatorcontrib><creatorcontrib>Winzeler, Elizabeth</creatorcontrib><creatorcontrib>Nussenzweig, Victor</creatorcontrib><title>Exposure of Plasmodium sporozoites to the intracellular concentration of potassium enhances infectivity and reduces cell passage activity</title><title>Molecular and biochemical parasitology</title><addtitle>Mol Biochem Parasitol</addtitle><description>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.</description><subject>Animals</subject><subject>Cell invasion</subject><subject>Cell Line</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Hepatocytes - parasitology</subject><subject>Host-Parasite Interactions</subject><subject>Humans</subject><subject>Kupffer Cells - parasitology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Plasmodium</subject><subject>Plasmodium berghei</subject><subject>Plasmodium berghei - drug effects</subject><subject>Plasmodium berghei - growth & development</subject><subject>Plasmodium berghei - pathogenicity</subject><subject>Plasmodium yoelii - drug effects</subject><subject>Plasmodium yoelii - growth & development</subject><subject>Plasmodium yoelii - pathogenicity</subject><subject>Potassium - pharmacology</subject><subject>Potassium shifts</subject><subject>Serial Passage</subject><subject>Sporozoites</subject><subject>Sporozoites - drug effects</subject><subject>Sporozoites - growth & development</subject><subject>Sporozoites - physiology</subject><issn>0166-6851</issn><issn>1872-9428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu3CAQhlGVKtls8woVp9y8ARsDPiZR0laK1B7aM8IwbljZxgEcJX2DvnWhu1KOkUZCGr5__tH8CGFKdpRQfrXfTX7snV900LuaELErRdgHtKFS1FXHanmCNhnlFZctPUPnMe4JIa3g_BSdUSEok6TdoL93L4uPawDsB_xj1HHy1q0TjosP_o93CSJOHqdHwG5OQRsYx3XUARs_Gyid5PxcxItPOsaihflR58-YFQOY5J5desV6tjiAXUu_DMFLpvVvwPpIfEIfBz1GuDi-W_Tr_u7n7dfq4fuXb7fXD5VhvEtVw1ptem4MF6TtDO17o2lnW9sMmlHB6t40UrNaNKwXpKFcNDVwyfuOcQu1abbo8jB3Cf5phZjU5GLZSM_g16i4rNtWEvYuSDsmmi57bJE8gCb4GAMMaglu0uFVUaJKXmqv3vJSJS9V6r_H56PH2k9g34THgDJwcwAgn-TZQVDROMjXtS7k2yrr3fsu_wBDdLAj</recordid><startdate>20071101</startdate><enddate>20071101</enddate><creator>Kumar, Kota Arun</creator><creator>Garcia, Celia R.S.</creator><creator>Chandran, Vandana R.</creator><creator>Van Rooijen, N.</creator><creator>Zhou, Yingyao</creator><creator>Winzeler, Elizabeth</creator><creator>Nussenzweig, Victor</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>F1W</scope><scope>FR3</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20071101</creationdate><title>Exposure of Plasmodium sporozoites to the intracellular concentration of potassium enhances infectivity and reduces cell passage activity</title><author>Kumar, Kota Arun ; 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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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>17714805</pmid><doi>10.1016/j.molbiopara.2007.07.004</doi><tpages>9</tpages></addata></record> |
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subjects | Animals Cell invasion Cell Line Cercopithecus aethiops COS Cells Hepatocytes - parasitology Host-Parasite Interactions Humans Kupffer Cells - parasitology Mice Mice, Inbred C57BL Plasmodium Plasmodium berghei Plasmodium berghei - drug effects Plasmodium berghei - growth & development Plasmodium berghei - pathogenicity Plasmodium yoelii - drug effects Plasmodium yoelii - growth & development Plasmodium yoelii - pathogenicity Potassium - pharmacology Potassium shifts Serial Passage Sporozoites Sporozoites - drug effects Sporozoites - growth & development Sporozoites - physiology |
title | Exposure of Plasmodium sporozoites to the intracellular concentration of potassium enhances infectivity and reduces cell passage activity |
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