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Given the indispensable role of heme, this auxotrophy may be exploited to develop drugs that interfere with heme uptake in parasites. Although multiple heme\u2010responsive genes (HRGs) have been characterized within the free\u2010living nematode\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , we have undertaken the first study of heme transport in\n                    <jats:italic>Brugia malayi<\/jats:italic>\n                    , a causative agent of lymphatic filariasis. Through functional assays in yeast, as well as heme analog, RNAi, and transcriptomic experiments, we have shown that the heme transporter\n                    <jats:italic>B. malayi<\/jats:italic>\n                    HRG\u20101 (BmHRG\u20101) is indeed functional in\n                    <jats:italic>B. malayi<\/jats:italic>\n                    . In addition,\n                    <jats:italic>Bm<\/jats:italic>\n                    HRG\u20101 localizes both to the endocytic compartments and cell membrane when expressed in yeast cells. Transcriptomic sequencing revealed that\n                    <jats:italic>Bm<\/jats:italic>\n                    HRG\u20101,\n                    <jats:italic>Bm<\/jats:italic>\n                    HRG\u20102, and\n                    <jats:italic>Bm<\/jats:italic>\n                    MRP\u20105 (all orthologs of HRGs in\n                    <jats:italic>C. elegans<\/jats:italic>\n                    ) are down\u2010regulated in heme\u2010treated\n                    <jats:italic>B. malayi<\/jats:italic>\n                    , as compared tonon\u2013heme\u2010treated control worms. Likely because of short gene lengths, multiple exons, other HRGs in\n                    <jats:italic>B. malayi<\/jats:italic>\n                    (BmHRG\u20103\u20136) remain unidentified. Although the precise mechanisms of heme homeostasis in a nematode with the ability to acquire heme remains unknown, this study clearly demonstrates that the filarial nematode\n                    <jats:italic>B. malayi<\/jats:italic>\n                    is capable of transporting exogenous heme.\u2014Luck, A. N., Yuan, X., Voronin, D., Slatko, B. E., Hamza, I., Foster, J. M. Heme acquisition in the parasitic filarial nematode\n                    <jats:italic>Brugia malayi<\/jats:italic>\n                    . FASEB J. 30, 3501\u20133514 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201600603r","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T22:28:20Z","timestamp":1467325700000},"page":"3501-3514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Heme acquisition in the parasitic filarial nematode\n                    <i>Brugia malayi<\/i>"],"prefix":"10.1096","volume":"30","author":[{"given":"Ashley N.","family":"Luck","sequence":"first","affiliation":[{"name":"New England BioLabs, Incorporated Genome Biology Division  Ipswich Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences University of Maryland  College Park Maryland USA"},{"name":"Department of Cell Biology and Molecular Genetics University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Voronin","sequence":"additional","affiliation":[{"name":"New York Blood Center Lindsley F. Kimball Research Institute  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barton E.","family":"Slatko","sequence":"additional","affiliation":[{"name":"New England BioLabs, Incorporated Genome Biology Division  Ipswich Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqbal","family":"Hamza","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences University of Maryland  College Park Maryland USA"},{"name":"Department of Cell Biology and Molecular Genetics University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy M.","family":"Foster","sequence":"additional","affiliation":[{"name":"New England BioLabs, Incorporated Genome Biology Division  Ipswich Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60586-7"},{"key":"e_1_2_8_3_1","article-title":"GPELF Progress Report 2000\u20132009 and Strategic Plan 2010\u20132020","author":"World Health Organization","year":"2010","journal-title":"WHO\/HTM\/NTD\/ PCT\/2010.6."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-2-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000998"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2009.11.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500877102"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1304049110"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030121"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023518"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003088"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06934"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.cell.2011.04.025","article-title":"An intercellular heme\u2010trafficking protein delivers maternal heme to the embryo during development in C","volume":"145","author":"Chen C.","year":"2011","journal-title":"elegans. 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