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dc.contributor.authorPunchi Hewage, Achala N. D.
dc.contributor.authorFontenot, Leo
dc.contributor.authorGuidry, Jessie
dc.contributor.authorWeldeghiorghis, Thomas
dc.contributor.authorMehta, Anil K.
dc.contributor.authorDonnarumma, Fabrizio
dc.contributor.authorRivera, Mario
dc.date.accessioned2022-01-17T19:27:03Z
dc.date.available2022-01-17T19:27:03Z
dc.date.issued2020-11-24
dc.identifier.citationPunchi Hewage, A.N.D.; Fontenot, L.; Guidry, J.; Weldeghiorghis, T.; Mehta, A.K.; Donnarumma, F.; Rivera, M. Mobilization of Iron Stored in Bacterioferritin Is Required for Metabolic Homeostasis in Pseudomonas aeruginosa. Pathogens 2020, 9, 980. https://doi.org/10.3390/pathogens9120980en_US
dc.identifier.urihttp://hdl.handle.net/1808/32409
dc.description.abstractIron homeostasis offers a significant bacterial vulnerability because pathogens obtain essential iron from their mammalian hosts, but host-defenses maintain vanishingly low levels of free iron. Although pathogens have evolved mechanisms to procure host-iron, these depend on well-regulated iron homeostasis. To disrupt iron homeostasis, our work has targeted iron mobilization from the iron storage protein bacterioferritin (BfrB) by blocking a required interaction with its cognate ferredoxin partner (Bfd). The blockade of the BfrB–Bfd complex by deletion of the bfd gene (Δbfd) causes iron to irreversibly accumulate in BfrB. In this study we used mass spectrometry and NMR spectroscopy to compare the proteomic response and the levels of key intracellular metabolites between wild type (wt) and isogenic ΔbfdP. aeruginosa strains. We find that the irreversible accumulation of unusable iron in BfrB leads to acute intracellular iron limitation, even if the culture media is iron-sufficient. Importantly, the iron limitation and concomitant iron metabolism dysregulation trigger a cascade of events that lead to broader metabolic homeostasis disruption, which includes sulfur limitation, phenazine-mediated oxidative stress, suboptimal amino acid synthesis and altered carbon metabolism.en_US
dc.publisherMDPIen_US
dc.rights© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectIron homeostasisen_US
dc.subjectIron metabolismen_US
dc.subjectSulfur metabolismen_US
dc.subjectPseudomonas aeruginosaen_US
dc.subjectFerritinen_US
dc.subjectBacterioferritinen_US
dc.subjectFerredoxinen_US
dc.subjectProteomicsen_US
dc.titleMobilization of Iron Stored in Bacterioferritin Is Required for Metabolic Homeostasis in Pseudomonas aeruginosaen_US
dc.typeArticleen_US
kusw.kuauthorPunchi Hewage, Achala N. D.
kusw.kudepartmentChemistryen_US
dc.identifier.doi10.3390/pathogens9120980en_US
dc.identifier.orcidhttps://orcid.org/ 0000-0003-3711-5162en_US
dc.identifier.orcidhttps://orcid.org/ 0000-0002-5601-0430en_US
dc.identifier.orcidhttps://orcid.org/ 0000-0003-1397-9919en_US
dc.identifier.orcidhttps://orcid.org/ 0000-0002-5692-5497en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC7760384en_US
dc.rights.accessrightsopenAccessen_US


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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Except where otherwise noted, this item's license is described as: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.