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dc.contributor.authorZygiel, Emily M
dc.contributor.authorObisesan, Adunoluwa O
dc.contributor.authorNelson, Cassandra E
dc.contributor.authorOglesby, Amanda G
dc.contributor.authorNolan, Elizabeth M
dc.date.accessioned2021-03-29T18:15:03Z
dc.date.available2021-03-29T18:15:03Z
dc.date.issued2021-01-04
dc.identifier.urihttp://hdl.handle.net/10713/15050
dc.description.abstractPseudomonas aeruginosa and Staphylococcus aureus are opportunistic bacterial pathogens that cause severe infections in immunocompromised individuals and patients with cystic fibrosis. Both P. aeruginosa and S. aureus require iron to infect the mammalian host. To obtain iron, these pathogens may rely on siderophore-mediated ferric iron uptake, ferrous iron uptake, or heme uptake at different points during infection. The preferred iron source depends on environmental conditions, including the presence of ironsequestering host-defense proteins. Here, we investigate how the presence of heme, a highly relevant iron source during infection, affects bacterial responses to iron withholding by the innate immune protein calprotectin (CP). Prior work has shown that P. aeruginosa is starved of iron in the presence of CP. We report that P. aeruginosa upregulates expression of heme uptake machinery in response to CP. Furthermore, we show that heme protects P. aeruginosa from CP-mediated inhibition of iron uptake and iron-starvation responses. We extend our study to a second bacterial pathogen, S. aureus, and demonstrate that CP also inhibits iron uptake and induces iron-starvation responses by this pathogen. Similarly to P. aeruginosa, we show that heme protects S. aureus from CP-mediated inhibition of iron uptake and iron-starvation responses. These findings expand our understanding of microbial responses to iron sequestration by CP and highlight the importance of heme utilization for bacterial adaptation to host iron-withholding strategies. © 2021 The Authors.en_US
dc.description.urihttps://doi.org/10.1074/jbc.RA120.015975en_US
dc.language.isoenen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.rightsPublished under license by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.subjectPseudomonas aeruginosa (P. aeruginosa)en_US
dc.subjectStaphylococcus aureus (S. aureus)en_US
dc.subjectcalprotectinen_US
dc.subjecthemeen_US
dc.subjectinnate immunityen_US
dc.subjectironen_US
dc.subjectnutritional immunityen_US
dc.titleHeme protects and from calprotectin-induced iron starvationen_US
dc.typeArticleen_US
dc.identifier.doi10.1074/jbc.RA120.015975
dc.identifier.pmid33273016
dc.source.countryUnited States


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