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Nevertheless, our understanding of how bacteria adapt their physiological condition to the tumor microenvironment remains elusive. In this work, we employed liquid chromatography-tandem mass spectrometry to examine the proteome of\n                    <jats:italic>E. coli<\/jats:italic>\n                    colonized in murine tumors. Compared to\n                    <jats:italic>E. coli<\/jats:italic>\n                    cultivated in the rich medium, we found that\n                    <jats:italic>E. coli<\/jats:italic>\n                    colonized in tumors notably upregulated the processes related to ferric ions, including the enterobactin biosynthesis and iron homeostasis. This finding indicated that the tumor is an iron-deficient environment to\n                    <jats:italic>E. coli<\/jats:italic>\n                    . We also found that the colonization of\n                    <jats:italic>E. coli<\/jats:italic>\n                    in the tumor led to an increased expression of lipocalin 2 (LCN2), a host protein that can sequester the enterobactin. We therefore engineered\n                    <jats:italic>E. coli<\/jats:italic>\n                    in order to evade the nutritional immunity provided by LCN2. By introducing the IroA cluster, the\n                    <jats:italic>E. coli<\/jats:italic>\n                    synthesizes the glycosylated enterobactin, which creates steric hindrance to avoid the LCN2 sequestration. The IroA-\n                    <jats:italic>E. coli<\/jats:italic>\n                    showed enhanced resistance to LCN2 and significantly improved the anti-tumor activity in mice. Moreover, the mice cured by the IroA-\n                    <jats:italic>E. coli<\/jats:italic>\n                    treatment became resistant to the tumor re-challenge, indicating the establishment of immunological memory. Overall, our study underscores the crucial role of bacteria\u2019s ability to acquire ferric ions within the tumor microenvironment for effective cancer therapy.\n                  <\/jats:p>","DOI":"10.7554\/elife.90798","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T09:07:09Z","timestamp":1695978429000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.90798","source":"Crossref","is-referenced-by-count":1,"title":["Overcoming the nutritional immunity by engineering iron-scavenging bacteria for cancer therapy"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1593-6511","authenticated-orcid":true,"given":"Sin-Wei","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bxb3784","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomedical Sciences, Academia Sinica","place":["Taipei, 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