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dc.contributor.authorZygiel, E.M.
dc.contributor.authorNelson, C.E.
dc.contributor.authorBrewer, L.K.
dc.date.accessioned2019-03-29T14:42:00Z
dc.date.available2019-03-29T14:42:00Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85062610814&doi=10.1074%2fjbc.RA118.006819&partnerID=40&md5=15de69edecdb0220f5f8b22740ba9721
dc.identifier.urihttp://hdl.handle.net/10713/8575
dc.description.abstractMost microbial pathogens have a metabolic iron requirement, necessitating the acquisition of this nutrient in the host. In response to pathogen invasion, the human host limits iron availability. Although canonical examples of nutritional immunity are host strategies that limit pathogen access to Fe(III), little is known about how the host restricts access to another biologically relevant oxidation state of this metal, Fe(II). This redox species is prevalent at certain infection sites and is utilized by bacteria during chronic infection, suggesting that Fe(II) withholding by the host may be an effective but unrecognized form of nutritional immunity. Here, we report that human calprotectin (CP; S100A8/S100A9 or MRP8/MRP14 heterooligomer) inhibits iron uptake and induces an iron starvation response in Pseudomonas aeruginosa cells by sequestering Fe(II) at its unusual His6 site. Moreover, under aerobic conditions in which the Fe(III) oxidation state is favored, Fe(II) withholding by CP was enabled by (i) its ability to stabilize this redox state in solution and (ii) the production and secretion of redox-active, P. aeruginosa-produced phenazines, which reduce Fe(III) to Fe(II). Analyses of the interplay between P. aeruginosa secondary metabolites and CP indicated that Fe(II) withholding alters P. aeruginosa physiology and expression of virulence traits. Lastly, examination of the effect of CP on cell-associated metal levels in diverse human pathogens revealed that CP inhibits iron uptake by several bacterial species under aerobic conditions. This work implicates CP-mediated Fe(II) sequestration as a component of nutritional immunity in both aerobic and anaerobic milieus during P. aeruginosa infection. © 2019 Zygiel et al.en_US
dc.description.urihttps://dx.doi.org/10.1074/jbc.RA118.006819en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.relation.ispartofThe Journal of biological chemistry
dc.subjectcalprotectinen_US
dc.subjectmetal homeostasisen_US
dc.subjectmetal sequestrationen_US
dc.subjectnutritional immunityen_US
dc.subjectphenazineen_US
dc.subject.meshBacteriaen_US
dc.subject.meshImmunity, Innateen_US
dc.subject.meshIronen_US
dc.subject.meshPseudomonas aeruginosaen_US
dc.subject.meshVirulenceen_US
dc.titleThe human innate immune protein calprotectin induces iron starvation responses in Pseudomonas aeruginosaen_US
dc.typeArticleen_US
dc.identifier.doi10.1074/jbc.RA118.006819
dc.identifier.pmid30622135


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