Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/26697
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Coombes, Brian K | - |
dc.contributor.author | Tsai, Caressa N | - |
dc.date.accessioned | 2021-07-28T18:54:04Z | - |
dc.date.available | 2021-07-28T18:54:04Z | - |
dc.date.issued | 2021 | - |
dc.identifier.uri | http://hdl.handle.net/11375/26697 | - |
dc.description.abstract | Salmonella enterica serovar Typhimurium (Salmonella) is a Gram-negative bacterial pathogen capable of causing both gastroenteritis and bacteraemia in human hosts. During infection, Salmonella invokes a complex network of virulence factors, regulatory systems, and metabolic pathways to promote immune evasion, sometimes demanding antibiotic treatment for resolution. Unfortunately, antibiotic resistance has reached critical levels in this and other pathogens, necessitating the discovery of new anti-infective targets and treatment options. Herein, we have sought to exploit the dynamic interactions between Salmonella and the host immune system to identify new, conditionally active anti-Salmonella therapies. In chapter 2, we aim to identify chemical compounds that are selectively antimicrobial against intracellular Salmonella, and discover that the anxiolytic drug metergoline inhibits Salmonella survival in cultured macrophages and systemically infected mice. In chapter 3, we screen for anti-virulence compounds that target regulatory signaling in Salmonella, and characterize the inhibitory activity of methyl-3,4-dephostatin, which perturbs SsrA/B and PmrB/A signaling and enhances sensitivity to colistin in vitro and in vivo. In chapter 4, we identify several host-directed compounds that modulate macrophage immunity and investigate their ability to attenuate a multidrug resistant Salmonella infection. Together, the work presented in this thesis demonstrates the potential for drug screening in infection-relevant conditions to identify new anti-infectives with non-traditional targets. | en_US |
dc.language.iso | en | en_US |
dc.subject | Salmonella | en_US |
dc.subject | antibiotic discovery | en_US |
dc.subject | innate immunity | en_US |
dc.subject | bacterial pathogenesis | en_US |
dc.title | Exploiting Host Immunity for Anti-infective Discovery in Salmonella Typhimurium | en_US |
dc.title.alternative | ANTI-INFECTIVE DISCOVERY IN SALMONELLA TYPHIMURIUM | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Tsai_Caressa_N_2021July_PhD.pdf | 11.59 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.