| dc.contributor |
Nolan, Elizabeth M. |
|
| dc.contributor |
Massachusetts Institute of Technology. Department of Chemistry |
|
| dc.creator |
Zygiel, Emily M. |
|
| dc.date |
2022-07-27T18:22:13Z |
|
| dc.date |
2022-07-27T18:22:13Z |
|
| dc.date |
2021-09 |
|
| dc.date |
2022-07-27T11:43:44.930Z |
|
| dc.date.accessioned |
2023-03-01T07:22:09Z |
|
| dc.date.available |
2023-03-01T07:22:09Z |
|
| dc.identifier |
https://hdl.handle.net/1721.1/144098 |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/275778 |
|
| dc.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. |
|
| dc.description |
Ph.D. |
|
| dc.format |
application/pdf |
|
| dc.publisher |
Massachusetts Institute of Technology |
|
| dc.rights |
In Copyright - Educational Use Permitted |
|
| dc.rights |
Copyright MIT |
|
| dc.rights |
http://rightsstatements.org/page/InC-EDU/1.0/ |
|
| dc.title |
Investigation of microbial responses to transition metal sequestration by the innate immune protein calprotectin |
|
| dc.type |
Thesis |
|