Ribosome Quality Control in Gram-Positive Bacteria

Protein production in bacteria, as in eukaryotes, is a complex, multistep process that presents many opportunities for error. In particular, ribosomes often pause or stall as they translate genetic code during protein manufacture. Ribosome stalling may result in errors or trigger rescue mechanisms needed to restart the process. The error-prone nature of cellular protein production makes it a promising target for antibiotics that might disrupt various mechanisms that bacteria have developed to ensure accurate translation of genetic material into proteins. Major gaps remain in our understanding of how gram-positive bacteria perform ribosome quality control, limiting our ability to disrupt or exploit weaknesses in ribosome rescue pathways.

Heather Feaga, Microbiology, is identifying and characterizing strategies used by gram-positive bacteria to detect and rescue stalled ribosomes. Using genetic, structural, and biochemical approaches, she and her team will investigate the physiological impacts of ribosome stalling in Bacillus subtilis and Bacillus anthracis. They will also determine how ribosome flexibility and atypical translation events, such as frameshifting and stop-codon read-through, can be used by gram-positive bacteria to increase coding capacity.

More than 200,000 infections per year in the United States are caused by antibiotic resistant gram-positive bacteria. This research investigates mechanisms by which gram-positive bacteria accurately and efficiently translate RNA into proteins. Knowledge gained from these studies will increase our understanding of essential ribosome rescue pathways and uncover new antibiotic targets.

NIH Award Number: 1R35GM147049-01

Cornell Researchers

Funding Received

$1.8 Million spanning 5 years