Kirienko, Natalia VBennett, George N2019-07-172019-07-172019-082019-06-04August 201Kang, Donghoon. "Biofilm-Mediated Regulation of Siderophore Production in Pseudomonas aeruginosa." (2019) Master’s Thesis, Rice University. <a href="https://hdl.handle.net/1911/106150">https://hdl.handle.net/1911/106150</a>.https://hdl.handle.net/1911/106150Pseudomonas aeruginosa is a gram-negative, multidrug-resistant, nosocomial pathogen that threatens the lives of immunocompromised patients. A key virulence factor in this pathogen is the siderophore pyoverdine. Due to its extremely high affinity for ferric iron, pyoverdine gives the pathogen a significant advantage over the host in their competition for iron. In addition, pyoverdine can regulate the production of multiple bacterial virulence factors and perturb host mitochondrial homeostasis. To elucidate the regulation of pyoverdine production, we developed a high-throughput genetic screen to identify genes necessary for its biosynthesis. Through this screen, we demonstrated that biofilm formation is necessary for pyoverdine production. Consistent with this result, upstream regulators of biofilm, notably intracellular c-di-GMP, regulated pyoverdine production in a biofilm-dependent manner. Furthermore, inhibiting biofilm formation using 2-amino-5,6-dimethylbenzimidazole was sufficient to attenuate pyoverdine production, suggesting that biofilm inhibitors may have multiple therapeutic benefits in addition to disrupting the pathogen’s main mechanism of antimicrobial resistance.application/pdfengCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.BiofilmPyoverdinePseudomonas aeruginosaAntivirulenceIron AcquisitionSiderophoresHigh-Throughput Screenc-di-GMPVirulenceCell AggregationThesis2019-07-17