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Article</a></font>  <b>|</b> <a href="/web/20070220143042/http://www.pnas.org/content/vol103/issue35/"><font size="-1" face="verdana,arial,helvetica,sans-serif">Table of Contents</font></a> <b>|</b>  <font size="-1" face="verdana,arial,helvetica,sans-serif"><a href="/web/20070220143042/http://www.pnas.org/cgi/content/short/103/35/13198">Next Article</a></font> <a href="/web/20070220143042/http://www.pnas.org/cgi/content/short/103/35/13198"><img src="/web/20070220143042im_/http://www.pnas.org/icons/toc/toc_arrownext.gif" border="0"></a> <p> <strong><font size="-2" color="A70716">BIOLOGICAL SCIENCES / MICROBIOLOGY</font></strong><br> <strong><font size="+2"> Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in <i>Toxoplasma gondii</i> </font></strong><p> <strong> </nobr><nobr>Jolly Mazumdar<sup>*</sup></nobr>, <nobr>Emma H. Wilson<sup><img src="/web/20070220143042im_/http://www.pnas.org/math/dagger.gif" alt="{dagger}" border="0"></sup></nobr>, <nobr>Kate Masek<sup><img src="/web/20070220143042im_/http://www.pnas.org/math/dagger.gif" alt="{dagger}" border="0"></sup></nobr>, <nobr>Christopher A. Hunter<sup><img src="/web/20070220143042im_/http://www.pnas.org/math/dagger.gif" alt="{dagger}" border="0"></sup></nobr>, and <nobr>Boris Striepen<sup>*</sup><sup>,<img src="/web/20070220143042im_/http://www.pnas.org/math/Dagger.gif" alt="{ddagger}" border="0"></sup><sup>,<img src="/web/20070220143042im_/http://www.pnas.org/math/link//sect.gif" alt="搂" border="0"></sup></nobr> </strong><p> *Department of Cellular Biology and <sup><img src="/web/20070220143042im_/http://www.pnas.org/math/Dagger.gif" alt="{ddagger}" border="0"></sup>Center for Tropical and Emerging Global Diseases, University of Georgia, Paul D. Coverdell Center, 500 D. W. Brooks Drive, Athens, GA 30602; and <sup><img src="/web/20070220143042im_/http://www.pnas.org/math/dagger.gif" alt="{dagger}" border="0"></sup>Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104 <p> Edited by Louis H. Miller, National Institutes of Health, Bethesda, MD, and approved July 5, 2006 (received for review April 26, 2006)<p> <p>  Apicomplexan parasites are the cause of numerous important human<sup> </sup>diseases including malaria and AIDS-associated opportunistic<sup> </sup>infections. Drug treatment for these diseases is not satisfactory<sup> </sup>and is threatened by resistance. The discovery of the apicoplast,<sup> </sup>a chloroplast-like organelle, presents drug targets unique to<sup> </sup>these parasites. The apicoplast-localized fatty acid synthesis<sup> </sup>(FAS II) pathway, a metabolic process fundamentally divergent<sup> </sup>from the analogous FAS I pathway in humans, represents one such<sup> </sup>target. However, the specific biological roles of apicoplast<sup> </sup>FAS II remain elusive. Furthermore, the parasite genome encodes<sup> </sup>additional and potentially redundant pathways for the synthesis<sup> </sup>of fatty acids. We have constructed a conditional null mutant<sup> </sup>of acyl carrier protein, a central component of the FAS II pathway<sup> </sup>in <i>Toxoplasma gondii</i>. Loss of FAS II severely compromises parasite<sup> </sup>growth in culture. We show FAS II to be required for the activation<sup> </sup>of pyruvate dehydrogenase, an important source of the metabolic<sup> </sup>precursor acetyl-CoA. Interestingly, acyl carrier protein knockout<sup> </sup>also leads to defects in apicoplast biogenesis and a consequent<sup> </sup>loss of the organelle. Most importantly, <i>in vivo</i> knockdown of<sup> </sup>apicoplast FAS II in a mouse model results in cure from a lethal<sup> </sup>challenge infection. In conclusion, our study demonstrates a<sup> </sup>direct link between apicoplast FAS II functions and parasite<sup> </sup>survival and pathogenesis. Our genetic model also offers a platform<sup> </sup>to dissect the integration of the apicoplast into parasite metabolism,<sup> </sup>especially its postulated interaction with the mitochondrion.<sup> </sup><p> <p><font size="-1">apicomplexa | fatty acid biosynthesis | lipoic acid | <i>Plasmodium</i> | plastid</font><p> <hr align="LEFT" width="50%" noshade size="1">  <a name=""></a> Author contributions: J.M. and B.S. designed research; J.M.,<sup> </sup>E.H.W., and K.M. performed research; J.M., E.H.W., C.A.H., and<sup> </sup>B.S. analyzed data; and J.M., C.A.H., and B.S. wrote the paper.<sup> </sup><p> <a name=""></a> Conflict of interest statement: No conflicts declared.<sup> </sup><p> <a name=""></a> This paper was submitted directly (Track II) to the PNAS office.<sup> </sup><p> <a name="COR1"></a> <sup><img src="/web/20070220143042im_/http://www.pnas.org/math/sect.gif" alt="搂" border="0"></sup>To whom correspondence should be addressed. E-mail: <span id="em0">striepen{at}cb.uga.edu</span><script type="text/javascript"></script><p>© 2006 by <a href="/web/20070220143042/http://www.pnas.org/misc/terms.shtml">The National Academy of Sciences</a> of the USA<p> <br clear="ALL"> <font face=""> </font> <br clear="ALL"> <br clear="ALL"> <br clear="ALL"> <br clear="ALL"> <table width="640" border="0" cellpadding="22" cellspacing="0"> <tr> <td><div align="center"> <p><a href="/web/20070220143042/http://www.pnas.org/current.shtml"><font size="1" face="Arial, Helvetica, sans-serif">Current Issue</font></a><font size="1" face="Arial, Helvetica, sans-serif"> | <a href="/web/20070220143042/http://www.pnas.org/contents-by-date.0.shtml">Archives</a> | <a href="/web/20070220143042/http://www.pnas.org/misc/onlinesubmission.shtml">Online Submission</a> | <a href="/web/20070220143042/http://www.pnas.org/misc/iforc.shtml">Info for Authors</a> | <a href="/web/20070220143042/http://www.pnas.org/misc/masthead.shtml">Editorial Board</a> | <a href="/web/20070220143042/http://www.pnas.org/misc/about.shtml">About</a> <br> <a href="/web/20070220143042/http://www.pnas.org/subscriptions/">Subscribe</a> | <a href="/web/20070220143042/http://www.pnas.org/misc/about.shtml#advertising">Advertise</a> | <a href="/web/20070220143042/http://www.pnas.org/cgi/feedback">Contact</a> | <a href="/web/20070220143042/http://www.pnas.org/misc/sitemap.shtml">Site Map</a></font></p> <p><font color="#660033" size="1" face="Arial, Helvetica, sans-serif"><a href="/web/20070220143042/http://www.pnas.org/misc/terms.shtml"><font color="#660033">Copyright © 2006 by the National Academy of Sciences</font></a> </font></p> </div></td> </tr> </table> <script src="https://web.archive.org/web/20070220143042js_/http://www.google-analytics.com/urchin.js" type="text/javascript"> </script> <script type="text/javascript"> _uacct = "UA-677185-1"; urchinTracker(); </script> </body> </html>