METAL TRAFFICKING DURING LIMITATION AND EXCESS IN BACILLUS SUBTILIS

Metal ions are essential for maintaining cellular life, as they are used as cofactors in many reactions and can be utilized as structural components of proteins. Metal ions are so important to bacteria that sequestering these metals is an antibacterial strategy employed by vertebrate immune systems. For example, human neutrophils and epithelial cells secrete calprotectin, an abundant antimicrobial protein, which has been shown to sequester zinc and iron from bacterial pathogens such as Staphylococcus aureus, preventing infection. In Bacillus subtilis, a model system for low G+C Gram-positive bacteria, zinc and iron are required for several essential processes. To maintain homeostasis of the concentrations of these metals, transcriptional regulators control gene expression to combat limitation and excess. Genes involved in responding to zinc excess are under the transcriptional control of CzrA, while genes involved in responding to zinc limitation are under the control of Zur. Zur derepresses genes in three distinct waves, one of which allows for the expression of the zinc importer ZnuABC and the metallochaperone ZagA. It is unknown how ZagA acquires zinc, where the zinc is chaperoned, or how metal transfer takes place. Here we discuss the idea that ZagA may acquire zinc from ZnuABC or zinc-containing ribosomal proteins. Potential clients of ZagA are also discussed. Genes involved in responding to iron limitation are controlled by Fur, and manganese homeostasis is controlled by the transcriptional repressor MntR, both of which control the expression of metal efflux systems. In addition, PerR is a transcriptional repressor that controls expression of PfeT, an iron efflux pump in response to peroxide stress. Here we show that PerR/Fur- and MntR-regulated efflux pumps (PfeT and MnePS, respectively) all contribute to iron efflux and metal ion homeostasis. Finally, this thesis touches upon basic statistical approaches in microbiology as well as a novel outreach program, Write a Researcher, that promotes diversity, equity, and inclusion in STEM by mentoring middle and high school students.

Name thesis:degree_name

Ph. D., Microbiology

Level thesis:degree_level

Doctor of Philosophy

Discipline thesis:degree_discipline

Microbiology

Grantor

Cornell University

Year dc:date.issued

2023

Author dc:creator

• Steingard, Caroline

Committee members dc:contributor.committeemember

• Doerr, Tobias
• Peters, Joseph

• Bacteria
• DEI
• Homeostasis
• Metals
• Outreach
• Regulation

Language dc:language.iso

en

DOI

https://doi.org/10.7298/bcsw-t474

Dc Identifier Other

ProQuest Submission ID: 13567
ProQuest Publication ID: 30425323

OAI identifier oai:identifier

oai:ecommons.cornell.edu:1813/114154