Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/29646Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Elliot, Marie | - |
| dc.contributor.author | Zambri, Matthew | - |
| dc.date.accessioned | 2024-04-11T19:08:18Z | - |
| dc.date.available | 2024-04-11T19:08:18Z | - |
| dc.date.issued | 2024 | - |
| dc.identifier.uri | http://hdl.handle.net/11375/29646 | - |
| dc.description.abstract | Streptomyces venezuelae employs two modes of development, classical growth and exploration. The newly described ‘exploratory’ growth occurs in response to glucose depletion and can occur in response to amino acid abundance. It begins with spore germination and vegetative outgrowth, but instead of then raising aerial hyphae and sporulating, S. venezuelae initiates rapid colony expansion that is driven by vegetative-like exploring hyphae. In classical development, vegetative hyphae grow by tip extension, which is mediated by the essential protein DivIVA. DivIVA localizes to the hyphal tips and recruits the cell wall biosynthetic machinery to drive growth at the cell poles. Our data indicate that while exploring hyphae are still polar-growing, DivIVA is subject to a novel proteolytic event during exploration. Furthermore, our investigations into the nature of the cell wall peptidoglycan of exploring cells have identified key changes to both its composition and structure. Specifically, the peptidoglycan isolated from explorers has a unique crosslinking pattern. Exploring cell walls further displayed remarkable structural plasticity; early-stage exploring cells have unusually thin hyphal walls that increase in thickness as exploration proceeds. Intriguingly, this cell wall thickening depends on MreB, a key shape-determining factor in many rod-shaped bacteria. mreB mutants exhibit defects in exploratory growth and increased cell lysis. In addition to having thinner cell walls, mreB mutants also have an altered peptidoglycan profile that suggests a disordered synthesis program and employ an unusual pattern of cell wall synthesis based on fluorescent D-amino acid incorporation. Our work is showing that S. venezuelae can radically reconfigure their cell wall construction from purely polar growth to a combination of polar growth and MreB-guided lateral wall insertion. This work reveals unprecedented flexibility in bacterial cell wall biosynthetic capabilities. | en_US |
| dc.language.iso | en | en_US |
| dc.title | Streptomyces venezuelae exploration: redefining growth in polar-growing bacteria | en_US |
| dc.type | Thesis | en_US |
| dc.contributor.department | Biology | en_US |
| dc.description.degreetype | Thesis | en_US |
| dc.description.degree | Doctor of Science (PhD) | en_US |
| dc.description.layabstract | Bacteria are encased in a meshwork of molecules called the cell wall. Though cell walls may differ in structure, they are extremely important for bacteria, providing them with protection from their environment, and conferring the structural support needed to both define and maintain their cell shape. As evidence of the importance of the bacterial cell wall, it is the target of many of our most important antibiotics (e.g. penicillin, vancomycin). Our organism of study, Streptomyces venezuelae, is a polar-growing bacterium: it builds its cell wall at the ends of their cells, guided by the protein DivIVA. This ‘polar growth’ mechanism is not universal amongst bacteria – not only can these microbes have different cell wall structures, they can also vary in the ways that they build them. In contrast to Streptomyces, many bacteria build their cell walls along the sides of their cells, instead of at the ends. For this, the protein MreB (instead of DivIVA) serves as the director of cell wall construction. Streptomyces also encode MreB but it has been shown to be involved in processes other than cell growth. We investigated MreB and its role in S. venezuelae growth in more detail and found that under particular growth conditions, MreB becomes essential for cell wall growth: we effectively showed that a polar-growing bacterium can also require side wall synthesis. We further discovered that this MreB-directed growth was accompanied by unexpected changes in cell wall thickness and compositional properties. Finally, we revealed that the end of the DivIVA protein (where DivIVA is the polar growth director) appears to be cut off when MreB becomes important – this modification of DivIVA has never before been reported. The conditions in which MreB activity and cutting of DivIVA occur during a specific mode of growth termed ‘exploration’. This exploration process was discovered relatively recently, and the conditions that stimulate it are still being uncovered. We have found that individual amino acids can have very different effects on exploration, with some promoting the early stages, and others fueling the later stages. iv Collectively, we described for the first time, a bacterium employing two entirely distinct ways of building their cell wall (both polar growth and side wall growth), a new mode of DivIVA control, and furthered our understanding of the growth conditions that influence exploratory growth. | en_US |
| Appears in Collections: | Open Access Dissertations and Theses | |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Zambri_Matthew_P_2024Mar_PhD.pdf | 5.21 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.
