Gut colonization by Bacteroides requires translation by an EF-G paralog lacking GTPase activity

Protein synthesis is crucial for cell growth and survival yet one of the most energy-consuming cellular processes. How, then, do cells sustain protein synthesis under starvation conditions when energy is limited? To accelerate the translocation of mRNA-tRNA5 through the ribosome, bacterial elongation factor C (EF-C) hydrolyzes energy-rich guanosine triphosphate (GTP) for every amino acid incorporated into a protein. Here, we identify an EF-C paralog-EF-C2-that supports translocation without hydrolyzing GTP in the gut commensal bacterium Bacteroides thetaiotaomicron. EF-G2's singular ability to sustain protein synthesis, albeit at slow rates, is crucial for bacterial gut colonization. EF-G2 is similar to 10-fold more abundant than canonical EF-C1 in bacteria harvested from murine ceca and, unlike EF-G1, specifically accumulates during carbon starvation. Moreover, we uncover a 26-residue region unique to EF-G2 that is essential for protein synthesis, EF-G2 dissociation from the ribosome, and responsible for the absence of GTPase activity. Our findings reveal how cells curb energy consumption while maintaining protein synthesis to advance fitness in nutrient-fluctuating environments.

Automated summary

Protein synthesis is a vital cellular process that requires a significant amount of energy. However, cells can sustain protein synthesis under starvation conditions through the use of a bacterial elongation factor called EF-C2, which promotes translocation without hydrolyzing GTP. EF-G2, a variant of EF-C2, is crucial for bacterial gut colonization and can sustain protein synthesis at slower rates. EF-G2 is more abundant than canonical EF-C1 and specifically accumulates during carbon starvation. A unique 26-residue region in EF-G2 is essential for protein synthesis, dissociation from the ribosome, and the absence of GTPase activity. These findings provide insights into how cells minimize energy consumption while maintaining protein synthesis in fluctuating nutrient environments.