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dc.contributor.advisorSulchek, Todd
dc.contributor.advisorBabensee, Julia
dc.contributor.advisorStowell, Sean
dc.contributor.authorBellavia, Michael
dc.date.accessioned2018-05-31T18:17:32Z
dc.date.available2018-05-31T18:17:32Z
dc.date.created2018-05
dc.date.issued2018-04-30
dc.date.submittedMay 2018
dc.identifier.urihttp://hdl.handle.net/1853/59955
dc.description.abstractHere we present bifunctional microparticles that bind Escherichia coli (E. coli) bacteria via a cell membrane constituent while also activating the classical complement pathway. Carboxylated polystyrene microparticles 1 µm in diameter were functionalized through several means with nonspecific polyclonal IgG and/or a monoclonal E. coli-binding antibody to compare different targeting schemes to localize complement to a particular bacterial strain. The complement-prompting polyclonal antibody was either adsorbed to saturate the particle nonspecifically (Untargeted, UT), adsorbed nonspecifically at half-saturation in combination with the targeting antibody (Mixed Untargeted, MUT), or interspersed amongst crosslinker-monoclonal antibody pairs formed such that the antibody Fab regions project outward (MT, Mixed Targeted). Cytotoxicity of each particle type to its cognate, either complement-sensitive non-pathogenic mutant E. coli J5 and wild-type pathogenic E. coli O157:H7 was evaluated, as was targeting affinity for anti-J5 particles and J5 bacteria. Although no type provided clinically-relevant cytotoxicity, notably the MUT particles were somewhat effective against the virulent and otherwise complement-resistant O157. Orienting the targeting moiety with the MT provided no benefit against either strain, and binding frequencies were attenuated relative to the MUT for J5 bacteria. Complement-sensitive J5 was most vulnerable to UT particles. In most cases, there was a correlation between increased cytotoxicity and the extent of IgG coverage, but this effect was generally not pronounced. Additional modifications to the MUT platform to more potently stimulate complement activation and a new base material for biocompatibility could enable its use as a sensitizer to be paired with antibiotics for systemic diseases such as sepsis or candidiasis.
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technology
dc.subjectClassical complement pathway
dc.subjectTargeted microparticles
dc.subjectAntibiotic resistance
dc.titleEvaluation of targeting schemes for complement-modulating, strain-selective antimicrobial microparticles
dc.typeThesis
dc.description.degreeM.S.
dc.contributor.departmentBiomedical Engineering (Joint GT/Emory Department)
thesis.degree.levelMasters
dc.date.updated2018-05-31T18:17:32Z


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