Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin
In response to microbial infection, the human host deploys metal-sequestering host-defense proteins to limit nutrient availability and thereby inhibit microbial growth and virulence. Calprotectin (CP) is an abundant antimicrobial protein that is released from neutrophils and epithelial cells at site...
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| Format: | Thesis |
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Massachusetts Institute of Technology
2022
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| Online Access: | https://hdl.handle.net/1721.1/144098 |
| _version_ | 1811097133767458816 |
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| author | Zygiel, Emily M. |
| author2 | Nolan, Elizabeth M. |
| author_facet | Nolan, Elizabeth M. Zygiel, Emily M. |
| author_sort | Zygiel, Emily M. |
| collection | MIT |
| description | In response to microbial infection, the human host deploys metal-sequestering host-defense proteins to limit nutrient availability and thereby inhibit microbial growth and virulence. Calprotectin (CP) is an abundant antimicrobial protein that is released from neutrophils and epithelial cells at sites of infection. CP sequesters divalent first-row transition metal ions and thereby limits the availability of essential metal nutrients in the extracellular space. The activity of CP has historically been understood from the standpoint of manganese and zinc withholding, but recent work has uncovered the ability of CP to bind iron and nickel. In this thesis, we investigate how iron and nickel withholding by CP contribute to its antimicrobial activity, and how microbes respond to the withholding of these nutrient metals. The work presented herein reveals changes to bacterial growth, cellular metal levels, metal starvation responses, and virulence characteristics in response to iron and nickel withholding by CP. Taken together, these recent contributions inform our current model for how CP contributes to metal homeostasis and immunity, and provide a foundation for further investigations of this remarkable metal-chelating protein at the host-microbe interface and beyond. |
| first_indexed | 2024-09-23T16:54:52Z |
| format | Thesis |
| id | mit-1721.1/144098 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:54:52Z |
| publishDate | 2022 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1440982022-07-28T03:00:49Z Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin Zygiel, Emily M. Nolan, Elizabeth M. Massachusetts Institute of Technology. Department of Chemistry In response to microbial infection, the human host deploys metal-sequestering host-defense proteins to limit nutrient availability and thereby inhibit microbial growth and virulence. Calprotectin (CP) is an abundant antimicrobial protein that is released from neutrophils and epithelial cells at sites of infection. CP sequesters divalent first-row transition metal ions and thereby limits the availability of essential metal nutrients in the extracellular space. The activity of CP has historically been understood from the standpoint of manganese and zinc withholding, but recent work has uncovered the ability of CP to bind iron and nickel. In this thesis, we investigate how iron and nickel withholding by CP contribute to its antimicrobial activity, and how microbes respond to the withholding of these nutrient metals. The work presented herein reveals changes to bacterial growth, cellular metal levels, metal starvation responses, and virulence characteristics in response to iron and nickel withholding by CP. Taken together, these recent contributions inform our current model for how CP contributes to metal homeostasis and immunity, and provide a foundation for further investigations of this remarkable metal-chelating protein at the host-microbe interface and beyond. Ph.D. 2022-07-27T18:22:13Z 2022-07-27T18:22:13Z 2021-09 2022-07-27T11:43:44.930Z Thesis https://hdl.handle.net/1721.1/144098 In Copyright - Educational Use Permitted Copyright MIT http://rightsstatements.org/page/InC-EDU/1.0/ application/pdf Massachusetts Institute of Technology |
| spellingShingle | Zygiel, Emily M. Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin |
| title | Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin |
| title_full | Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin |
| title_fullStr | Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin |
| title_full_unstemmed | Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin |
| title_short | Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin |
| title_sort | investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin |
| url | https://hdl.handle.net/1721.1/144098 |
| work_keys_str_mv | AT zygielemilym investigationofmicrobialresponsestotransitionmetalsequestrationbytheinnateimmuneproteincalprotectin |