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Molecular signatures required for type VIIb secretion system substrate export

dc.contributor.advisorWhitney, John C.
dc.contributor.authorShah, Prakhar Y.
dc.contributor.departmentBiochemistry and Biomedical Sciencesen_US
dc.date.accessioned2024-08-28T15:14:22Z
dc.date.available2024-08-28T15:14:22Z
dc.date.issued2024
dc.description.abstractMost bacteria live in densely colonized environments and are in constant competition for space and nutrients. The result of this competition is an ‘arms race’ in which various strategies for bacterial inhibition have evolved, such as the bacterial type VII secretion system (T7SS), directly inject toxins into competitor bacteria. The T7SS is a macromolecular machine unique to the Gram-positive phyla Actinobacteria and Firmicutes and is further divided into genetically distinct subtypes denoted T7SSa and T7SSb, respectively. The T7SSa is well-characterized in Mycobacteria, however, the T7SSb remains understudied. These two systems share a conserved membrane-embedded ATPase and the secretion of small α-helical proteins (called “effectors”), some of which are toxic and drive bacterial pathogenicity by facilitating microbe-microbe and host-microbe interactions. My graduate thesis seeks to determine the secretion mechanism of T7SSb effectors in the genus Streptococcus. This includes characterization of chaperones that directly interact with the effectors and mediate their export. Insights from understanding the molecular signatures that dictate effector export will help determine the apparatus component that recognizes these signatures and facilitates effector transport through the apparatus. This will provide significant inroads into understanding the type VIIb secretion mechanism.en_US
dc.description.degreeMaster of Science (MSc)en_US
dc.description.degreetypeThesisen_US
dc.description.layabstractBacteria are typically found in communities, which at times face limited resources in terms of both nutrients to grow on and space to multiply. This environmental pressure causes bacteria to compete with other neighbouring bacteria. To gain a fitness advantage, bacteria have evolved strategies to kill one another to have sole access to the resources available. One such strategy is the type VIIb secretion system, which delivers antibacterial toxins directly into competing Gram-positive bacteria. For this body of work, I investigate two parts of the type VIIb secretion system export mechanism including: (1) what molecular signature commits toxins to export through the type VII secretion system; and (2) how components of the type VII secretion system recognize the toxin signature to allow export. These investigations will help understand the entirety of the type VIIb secretion mechanism.en_US
dc.identifier.urihttp://hdl.handle.net/11375/30108
dc.language.isoenen_US
dc.titleMolecular signatures required for type VIIb secretion system substrate exporten_US
dc.title.alternativeType VIIb secretion system substrate exporten_US
dc.typeThesisen_US

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