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Ni\n                    <jats:sup>2+<\/jats:sup>\n                    is an essential cofactor in urease and [NiFe]-hydrogenases involved in colonization and persistence. Many microbes produce metallophores to sequester metals necessary for their metabolism and starve competing neighboring organisms. The fungal metallophore aspergillomarasmine A (AMA) shows narrow specificity for Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , Ni\n                    <jats:sup>2+<\/jats:sup>\n                    , and Co\n                    <jats:sup>2+<\/jats:sup>\n                    . Here, we show that this specificity allows AMA to block the uptake of Ni\n                    <jats:sup>2+<\/jats:sup>\n                    and attenuate bacterial Ni-dependent enzymes, offering a potential strategy for reducing virulence. Bacterial exposure to AMA perturbs H\n                    <jats:sub>2<\/jats:sub>\n                    metabolism, ureolysis, struvite crystallization, and biofilm formation and shows efficacy in a\n                    <jats:italic>Galleria mellonella<\/jats:italic>\n                    animal infection model. The inhibition of Ni-dependent enzymes was aided by Zn\n                    <jats:sup>2+,<\/jats:sup>\n                    which complexes with AMA and competes with the native nickelophore for the uptake of Ni\n                    <jats:sup>2+<\/jats:sup>\n                    . Biochemical analyses demonstrated high-affinity binding of AMA-metal complexes to NikA, the periplasmic substrate-binding protein of the Ni\n                    <jats:sup>2+<\/jats:sup>\n                    uptake system. Structural examination of NikA in complex with Ni-AMA revealed that the coordination geometry of Ni-AMA mimics the native ligand, Ni-(\n                    <jats:sc>l<\/jats:sc>\n                    -His)\n                    <jats:sub>2<\/jats:sub>\n                    , providing a structural basis for binding AMA-metal complexes. Structure-activity relationship studies of AMA identified regions of the molecule that improve NikA affinity and offer potential routes for further developing this compound as an anti-virulence agent.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-48232-1","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:02:09Z","timestamp":1715608929000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes"],"prefix":"10.1038","volume":"15","author":[{"given":"David","family":"Sychantha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6446-9567","authenticated-orcid":false,"given":"Kalinka","family":"Koteva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-7533","authenticated-orcid":false,"given":"Gerd","family":"Prehna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9129-7131","authenticated-orcid":false,"given":"Gerard D.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"48232_CR1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0168-6445(03)00042-1","volume":"27","author":"SB Mulrooney","year":"2003","unstructured":"Mulrooney, S. 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