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

Abstract

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–tRNAs through the ribosome, bacterial elongation factor G (EF‐G) hydrolyzes energy‐rich guanosine triphosphate (GTP) for every amino acid incorporated into a protein. Here, we identify an EF‐G paralog—EF‐G2—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 ~10‐fold more abundant than canonical EF‐G1 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. image Gut‐commensal Bacteroides thetaiotaomicron harbors a second paralog of translation elongation factor EF‐G, EF‐G2. Here, EF‐G2 is found to increase bacterial fitness in the nutrient‐fluctuating gut environment by mediating slow translation without GTP hydrolysis. EF‐G2 is abundant specifically during carbon starvation when energy is limited. EF‐G2 promotes ribosome translocation and protein synthesis without consuming GTP. A unique insert conserved in all Bacteroides dictates EF‐G2's energy‐saving activity. Protein synthesis mediated by EF‐G2 is essential for gut colonization.