Ribosome inactivation by Escherichia coli GTPase RsgA inhibits T4 phage

Introduction: Bacteria must combat phages, and myriad bacterial anti-phage systems have been discovered that reduce host metabolism, for example, by depleting energetic compounds like ATP and NAD⁺. Hence, these systems indirectly inhibit protein production. Surprisingly, direct reduction of ribosome activity has not been demonstrated to thwart phage. Methods: Here, by producing each of the 4,287 Escherichia coli proteins and selecting for anti-phage activity that leads to enhanced growth, we investigated the role of host proteins in phage inhibition. Results and discussion: We identified that E. coli GTPase RsgA inhibits lytic phage T4 by inactivating ribosomes.