UC San Diego

Antibiotic metabolites play a major role in the interactions between prokaryotes and eukaryotes. The exact effect of these antibiotics can be difficult to study due to the complexity of microbial communities and dynamics, as well as environmental conditions that differ from laboratory ones. Here, I employ Bacterial Cytological Profiling, an unbiased microscopy-based technique able to determine the mechanism of action of an antibiotic within hours. In Chapter 1, I have discovered using BCP that a family of plant defense metabolites called the flavones exhibits nontraditional structure-activity relationships, where minor modifications made to the flavone backbone alter their antibiotic mechanism of action, as well as discover new antibiotic MOAs previous unattributed to flavones. I also employ BCP in Chapter 2 to study fungal-bacterial interactions on Cheese Curd Agar, and identify the nature of fungal inhibition of bacterial growth in microbial cheese communities. Finally, in Chapter 3, I use BCP to analyze the drug SCH79797, to show a dual effect of boosting neutrophil killing in vivo as well as having direct antibacterial activity, highlighting the complexity of studying the effects of molecules in eukaryotic environments. Overall, these studies provide insight into the prokaryotic-eukaryotic interface, as well as provide proof-of-concept studies for the development of in situ techniques to analyze antibiotic activities in non-laboratory settings.