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dc.contributor.authorRobertson, Peter
dc.date.accessioned2016-08-31T15:52:13Z
dc.date.available2016-08-31T15:52:13Z
dc.identifier.urihttp://hdl.handle.net/10222/72155
dc.description.abstractLegionella pneumophila is a ubiquitous freshwater pathogen of unicellular eukaryotes, namely several species of amoeba. Following inhalation of Legionella-contaminated aerosols, susceptible human populations may also develop an atypical, pneumonia-like illness, as L. pneumophila opportunistically infects alveolar macrophages. One of the many virulence factors possessed by L. pneumophila is High Temperature Protein B (HtpB), a multifunctional chaperonin that has been found on the cell surface. Despite the several virulence-related roles that have been described for the surface-exposed or extracellularly released HtpB, no mechanism has yet been proposed for how this essential, typically cytoplasmic protein reaches extracytoplasmic compartments. In this work, we present evidence that Dot/Icm, a type IV secretion system of L. pneumophila, is responsible for the translocation of HtpB through a non-canonical secretion pathway. An infection model using L. pneumophila carrying a genetically tagged, recombinant HtpB demonstrated that HtpB does not reach the cytoplasm of Legionella-infected host cells without a functional Dot/Icm system. By fusing the C-terminus of HtpB to the cytoplasmic protein Icd and assaying its sub-cellular locale by western blotting, we demonstrate that the C-terminus of HtpB has affinity for the Legionella envelope membranes but is not sufficient to mediate secretion. These results, as well as prior data generated by other researchers/students in the Garduño Lab at Dalhousie University, led us to conclude that HtpB normally traffics through the periplasm of L. pneumophila and relies on the Dot/Icm system for escaping the periplasm, but crosses the inner membrane in an uncharacterized manner. This unknown mechanism by which HtpB seems to translocate across the cytoplasmic membrane may apply to other Legionella proteins and thus contribute to explain the unusual quantity and diversity of Dot/Icm effectors, therefore being of critical importance to the understanding of virulence in L. pneumophila.en_US
dc.language.isoenen_US
dc.subjectBacteriologyen_US
dc.subjectSecretionen_US
dc.subjectLegionellaen_US
dc.subjectChaperoninen_US
dc.titleInvestigating the Secretion of HtpB, the Multifunctional Chaperonin of Legionella pneumophilaen_US
dc.typeThesisen_US
dc.date.defence2016-08-17
dc.contributor.departmentDepartment of Microbiology & Immunologyen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.external-examinerDr. John Archibalden_US
dc.contributor.graduate-coordinatorDr. Brent Johnstonen_US
dc.contributor.thesis-readerDr. Song Leeen_US
dc.contributor.thesis-supervisorDr. Rafael Gardunoen_US
dc.contributor.thesis-supervisorDr. Jason LeBlancen_US
dc.contributor.ethics-approvalNot Applicableen_US
dc.contributor.manuscriptsNot Applicableen_US
dc.contributor.copyright-releaseYesen_US
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