(253f) Establishing the Biogenesis Process for a Bacterial Organelle

Identification of novel antibiotic targets is crucial in combatting the growing threat of antibiotic resistance. Ideal targets for antibiotic development are those that specifically exist in pathogenic bacteria, but not healthy biota. Bacterial microcompartments (MCPs) are proteinaceous organelles that specifically aide in the proliferation of enteric pathogens on niche carbon sources, and thus represent excellent candidates for targeted antibiotic development. These MCPs are delimited by a protein shell that encases an enzymatic core, where the core enzymes are responsible for carrying out metabolic processes that aide in proliferation. An abundance of protein-protein interactions (PPIs) are responsible for holding together the MCP shell; however, development of inhibitors against the interactions that make up the MCP has been limited by knowledge of which interactions are essential for proper MCP function.

In this talk, I will describe our recent discovery of the three processes essential to proper formation of the 1,2-propanediol utilization (Pdu) MCP from model pathogen Salmonella enterica serovar Typhimurium LT2, and which essential proteins are required for these processes. Further, I will describe how we have used computational modeling tools to understand how different perturbations to the assembly state of the Pdu MCP impact the ability of MCPs to confer benefits to cell metabolism, and how we corroborated these results with experiments. Combined, this information provides a comprehensive picture of the Pdu MCP assembly process, setting the stage for which PPIs we should target for future antibiotic discovery.