Daniel Srole Rose Hills
Structural Basis of Macrolide Sensitivity and its Impacts on Antibiotic Design and Use
With our overuse of antibiotics and the resulting decline in their effectiveness, it has become increasingly important to understand their mechanisms of action. Many antibiotics act on harmful bacteria by targeting ribosomal processes and disrupting the translation from mRNA to proteins, thereby interrupting gene expression. The cells abilities to function and reproduce are thereby disrupted, and we observe the desired effects of antibiotics rather quickly. Macrolides are a class of antibiotic that works in this way. The binding site for these molecules in prokaryotes is highly conserved in eukaryotes. With such a large similarity, it is not known exactly why eukaryotes are resistant to their effects. No prior research has found the structural basis that confers macrolide sensitivity to prokaryotes but not to eukaryotes. By probing the macrolide binding pocket in both, I hope to discover mutations that remove macrolide sensitivity in prokaryotes as well as those that confer it in eukaryotes. If successful, we will be able to piece together an understanding of macrolide function.