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Here, we show that the fungus <jats:italic>Candida albicans<\/jats:italic> sequesters essential magnesium ions from the bacterium <jats:italic>Pseudomonas aeruginosa<\/jats:italic>. To counteract fungal Mg<jats:sup><jats:bold>2<\/jats:bold>+<\/jats:sup> sequestration, <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic> expresses the Mg<jats:sup><jats:bold>2<\/jats:bold>+<\/jats:sup> transporter MgtA when Mg<jats:sup><jats:bold>2<\/jats:bold>+<\/jats:sup> levels are low. Thus, loss of MgtA specifically impairs <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic> in co-culture with <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic>, but fitness can be restored by supplementing Mg<jats:sup><jats:bold>2<\/jats:bold>+<\/jats:sup>. Using a panel of fungi and bacteria, we show that Mg<jats:sup><jats:bold>2<\/jats:bold>+<\/jats:sup> sequestration is a general mechanism of fungal antagonism against gram-negative bacteria. Mg<jats:sup><jats:bold>2<\/jats:bold>+<\/jats:sup> limitation enhances bacterial resistance to polymyxin antibiotics like colistin, which target gram-negative bacterial membranes. Indeed, experimental evolution reveals that <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic> evolves <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic>-dependent colistin resistance via non-canonical means; antifungal treatment renders resistant bacteria colistin-sensitive. Our work suggests that fungal\u2013bacterial competition could profoundly impact polymicrobial infection treatment with antibiotics of last resort.<\/jats:p>","DOI":"10.1371\/journal.pbio.3002694","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T17:45:00Z","timestamp":1718905500000},"page":"e3002694","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Widespread fungal\u2013bacterial competition for magnesium lowers bacterial susceptibility to polymyxin antibiotics"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-3873","authenticated-orcid":true,"given":"Yu-Ying Phoebe","family":"Hsieh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet 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