Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation
Pseudomonas 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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2022
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| Online Access: | https://hdl.handle.net/1721.1/141194 |
| _version_ | 1826202050402189312 |
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| author | Zygiel, Emily M Obisesan, Adunoluwa O Nelson, Cassandra E Oglesby, Amanda G Nolan, Elizabeth M |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Zygiel, Emily M Obisesan, Adunoluwa O Nelson, Cassandra E Oglesby, Amanda G Nolan, Elizabeth M |
| author_sort | Zygiel, Emily M |
| collection | MIT |
| description | Pseudomonas 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. |
| first_indexed | 2024-09-23T12:01:25Z |
| format | Article |
| id | mit-1721.1/141194 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:01:25Z |
| publishDate | 2022 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1411942023-06-22T18:48:58Z Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation Zygiel, Emily M Obisesan, Adunoluwa O Nelson, Cassandra E Oglesby, Amanda G Nolan, Elizabeth M Massachusetts Institute of Technology. Department of Chemistry Pseudomonas 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. 2022-03-15T18:09:13Z 2022-03-15T18:09:13Z 2021 2022-03-15T18:03:32Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141194 Zygiel, Emily M, Obisesan, Adunoluwa O, Nelson, Cassandra E, Oglesby, Amanda G and Nolan, Elizabeth M. 2021. "Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation." Journal of Biological Chemistry, 296. en 10.1074/JBC.RA120.015975 Journal of Biological Chemistry Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Zygiel, Emily M Obisesan, Adunoluwa O Nelson, Cassandra E Oglesby, Amanda G Nolan, Elizabeth M Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation |
| title | Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation |
| title_full | Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation |
| title_fullStr | Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation |
| title_full_unstemmed | Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation |
| title_short | Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation |
| title_sort | heme protects pseudomonas aeruginosa and staphylococcus aureus from calprotectin induced iron starvation |
| url | https://hdl.handle.net/1721.1/141194 |
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