{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:14:57Z","timestamp":1790162097978,"version":"4.1.0"},"reference-count":245,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"Narodowym Centrum Nauki","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Iron is an essential micronutrient for most living organisms, but its bioavailability is limited. To facilitate iron uptake, many bacteria and fungi secrete siderophores, which are small, high-affinity iron-chelating molecules. Siderophores play a key role in microbial competition and immune evasion, and additionally serve as an entry point for bacteriophages and toxins. Ferrichrome, a well-studied fungal hydroxamate siderophore, is utilized as an iron source by numerous bacterial species, including human-associated and pathogenic bacteria. Ferrichrome is a cyclic hexapeptide composed of three glycine residues and three N\n                    <jats:sup>5<\/jats:sup>\n                    -acetyl-N\n                    <jats:sup>5<\/jats:sup>\n                    -hydroxy-L-ornithine residues, which provide hydroxamate groups that are responsible for iron chelation. Synthetic strategies for desferrichrome and hydroxamate siderophore scaffolds were developed over time allowing the utilization of orthogonally protected hydroxyornithine building blocks. Modern orthogonal solid-phase peptide synthesis supports structural investigation and allows precise functionalization for the design of ferrichrome analogs. Inspired by naturally occurring siderophore-antibiotic conjugates that exploit siderophore uptake pathways to enter bacterial cells, synthetic ferrichrome or ferrichrome mimics have been coupled to a variety of antibacterial moieties. Ferrichrome conjugation to antibiotics improved bacterial uptake and achieved MICs in the nanomolar range. Ga-complexed ferrichrome mimics did not perturb expression of siderophore-transport genes and showed even higher antibacterial activity. In a proof-of-concept study, antisense oligonucleotides coupled to ferrichrome analogs were transported into\n                    <jats:italic>E. coli<\/jats:italic>\n                    and gene silencing could be monitored by a decrease in fluorescence. Ferrichrome has also been employed as a metal chelator in preclinical zirconium- and gallium-based PET imaging agents.\n                    <jats:sup>68<\/jats:sup>\n                    Ga-ferrirubin demonstrated favorable properties for imaging bacterial infection caused by\n                    <jats:italic>S. aureus<\/jats:italic>\n                    and\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    . Ferrichrome has exhibited antitumor activity against different tumor entities\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in murine xenograft models. The mechanistic background of the antitumor effects is not yet comprehensively understood and the investigation of immune effects is hampered by the restricted choice of suitable\n                    <jats:italic>in vivo<\/jats:italic>\n                    models. Overall, ferrichrome and its mimics are versatile molecules with strong potential for analytical and therapeutic applications, but further preclinical studies are required in the respective fields to establish the suitability of the molecules.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1932981","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:45:04Z","timestamp":1790160304000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ferrichrome: bacterial function, synthetic mimics, and biomedical applications"],"prefix":"10.3389","volume":"17","author":[{"given":"Nicolas","family":"R\u00e4ther","sequence":"first","affiliation":[{"name":"Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock","place":["Rostock, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Wojciechowska","sequence":"additional","affiliation":[{"name":"Centre of New Technologies, University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Trylska","sequence":"additional","affiliation":[{"name":"Centre of New Technologies, University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Patenge","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock","place":["Rostock, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.nucmedbio.2010.12.011","article-title":"In vivo biodistribution and accumulation of 89Zr in mice","volume":"38","author":"Abou","year":"2011","journal-title":"Nucl. 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