{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:28:09Z","timestamp":1775582889388,"version":"3.50.1"},"posted":{"date-parts":[[2024,12,21]]},"group-title":"Developmental Biology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The diverse microbiota of the intestine is expected to benefit the host, yet the beneficial metabolites derived from the microbiota are still poorly understood. Enterobactin (Ent) is a well- known secreted iron-scavenging siderophore made by bacteria to fetch iron from the host or environment. Little was known about a positive role of Ent until a recent discovery in the nematode\n                  <jats:italic>C. elegans<\/jats:italic>\n                  indicated a beneficial role of Ent in promoting mitochondrial iron level in the animal intestine. To solidify this new paradigm, we further tested this role in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  and multiple mammalian cell models and its relationship with the primary iron transporter DMT1\/SMF-3 and several other iron-related genes. Here we show that ferric enterobactin (FeEnt) supplementation promotes whole organism development in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  , increases iron uptake in caco-2 human intestinal epithelial cells, and supports iron-dependent differentiation of murine erythroid progenitor cells, indicating that the FeEnt complex can effectively enter these cells and be bioavailable. Our data in multiple models demonstrate that FeEnt-mediated iron transport is independent of all tested iron transporters. In addition, FeEnt supplementation robustly suppresses the developmental defects of a\n                  <jats:italic>hif-1<\/jats:italic>\n                  mutant under low iron condition, suggesting the critical role in iron homeostasis for this well-known hypoxia regulator. These results suggest that FeEnt can effectively enter animal cells and their mitochondria through a previously unknown mechanism that may be leveraged as a therapeutic ferric iron carrier for the treatment of DMT1- or HIF-1-related iron deficiency and anemia.\n                <\/jats:p>","DOI":"10.1101\/2024.12.20.629725","type":"posted-content","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T21:20:18Z","timestamp":1734816018000},"source":"Crossref","is-referenced-by-count":1,"title":["Enterobactin carries iron into\n                  <i>C. elegans<\/i>\n                  and mammalian intestinal cells by a mechanism independent of divalent metal transporter DMT1"],"prefix":"10.64898","author":[{"given":"Aileen K.","family":"Sewell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxue","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengnan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda R.","family":"Host","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024122401301627000_2024.12.20.629725v1.1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00502a053"},{"key":"2024122401301627000_2024.12.20.629725v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0630018100"},{"key":"2024122401301627000_2024.12.20.629725v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.10.005"},{"key":"2024122401301627000_2024.12.20.629725v1.4","doi-asserted-by":"publisher","DOI":"10.1021\/ja00514a037"},{"key":"2024122401301627000_2024.12.20.629725v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11508-y"},{"key":"2024122401301627000_2024.12.20.629725v1.6","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b09375"},{"key":"2024122401301627000_2024.12.20.629725v1.7","doi-asserted-by":"publisher","DOI":"10.1039\/b906679a"},{"key":"2024122401301627000_2024.12.20.629725v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio771"},{"key":"2024122401301627000_2024.12.20.629725v1.9","doi-asserted-by":"publisher","DOI":"10.1021\/cb0500034"},{"key":"2024122401301627000_2024.12.20.629725v1.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1811314"},{"key":"2024122401301627000_2024.12.20.629725v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.020"},{"key":"2024122401301627000_2024.12.20.629725v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.032"},{"key":"2024122401301627000_2024.12.20.629725v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.07.020"},{"key":"2024122401301627000_2024.12.20.629725v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.01.021"},{"key":"2024122401301627000_2024.12.20.629725v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.034"},{"key":"2024122401301627000_2024.12.20.629725v1.16","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-240564"},{"key":"2024122401301627000_2024.12.20.629725v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18584-4"},{"key":"2024122401301627000_2024.12.20.629725v1.18","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.13.3823"},{"key":"2024122401301627000_2024.12.20.629725v1.19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007792"},{"key":"2024122401301627000_2024.12.20.629725v1.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002394"},{"key":"2024122401301627000_2024.12.20.629725v1.21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44674"},{"key":"2024122401301627000_2024.12.20.629725v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-019-0504-y"},{"key":"2024122401301627000_2024.12.20.629725v1.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.2844"},{"key":"2024122401301627000_2024.12.20.629725v1.24","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301133"},{"key":"2024122401301627000_2024.12.20.629725v1.25","doi-asserted-by":"publisher","DOI":"10.1024\/0300-9831\/a000038"},{"key":"2024122401301627000_2024.12.20.629725v1.26","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20180939"},{"key":"2024122401301627000_2024.12.20.629725v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2006.08.005"},{"key":"2024122401301627000_2024.12.20.629725v1.28","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051987"},{"key":"2024122401301627000_2024.12.20.629725v1.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.2.378"},{"key":"2024122401301627000_2024.12.20.629725v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/35042073"},{"key":"2024122401301627000_2024.12.20.629725v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.04.010"},{"key":"2024122401301627000_2024.12.20.629725v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.03.003"},{"key":"2024122401301627000_2024.12.20.629725v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13430"},{"key":"2024122401301627000_2024.12.20.629725v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/nature18849"},{"key":"2024122401301627000_2024.12.20.629725v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/nature03104"},{"key":"2024122401301627000_2024.12.20.629725v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.10.489"},{"key":"2024122401301627000_2024.12.20.629725v1.37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071816-064559"},{"key":"2024122401301627000_2024.12.20.629725v1.38","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1823801"},{"key":"2024122401301627000_2024.12.20.629725v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32594-0"},{"key":"2024122401301627000_2024.12.20.629725v1.40","doi-asserted-by":"publisher","DOI":"10.1007\/BF01135388"},{"key":"2024122401301627000_2024.12.20.629725v1.41","doi-asserted-b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