Mechanism of Action and Efficacy of Antibacterial ChemBridge Compounds

Undergraduate Honors Thesis

Citations

Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/nc580p12z

Abstract

Current efforts to develop antibiotics are not keeping up with the need for new antimicrobials due to the increasing prevalence of antibiotic resistance. This is especially problematic for infections with Gram-negative and intracellular bacteria, which are harder for antimicrobials to access due to the structure of the double membrane envelope. One way to combat this issue is to find antibiotics that synergize with the immune insults found within host cells. A screen designed in this manner has uncovered three structurally related antibacterial molecules termed “the Class 1 compounds.”

Elucidation of the mechanism of action of these compounds could provide valuable insights about potential new antibiotic targets. Previous work has shown that the Class 1 compounds likely affect the inner membrane. Further investigation has revealed that the compounds disrupt bacterial membrane voltage without permeabilizing the inner membrane, but not to an extent that causes voltage-dependent proteins to be mislocalized. Additionally, the compounds are not effective in a Galleria mellonella waxworm infection model and do not affect macrophage cytokine release.

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