Ribosome inactivation by Escherichia coli GTPase RsgA inhibits T4 phage

Laura Fernández-García; María Tomás; Thomas K Wood

doi:10.3389/fmicb.2023.1242163

Ribosome inactivation by Escherichia coli GTPase RsgA inhibits T4 phage

Front Microbiol. 2023 Aug 21:14:1242163. doi: 10.3389/fmicb.2023.1242163. eCollection 2023.

Authors

Laura Fernández-García^{1

2}, María Tomás², Thomas K Wood¹

Affiliations

¹ Department of Chemical Engineering, Pennsylvania State University, University Park, PA, United States.
² Microbiology Translational and Multidisciplinary (MicroTM)-Research Institute Biomedical A Coruña (INIBIC) and Microbiology Department of Hospital A Coruña (CHUAC), University of A Coruña (UDC), A Coruña, Spain.

Abstract

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.

Keywords: RsgA; persistence; phage inhibition; ribosome inactivation; ribosomes.

Grants and funding

This work was supported by both a Fulbright Scholar Fellowship and a Xunta de Galicia Postdoctoral Grant for LF-G. This study has been funded by the Instituto de Salud Carlos III (ISCIII) through projects PI19/00878 and PI22/00323 and co-funded by the European Union, by a Personalized and Precision Medicine Grant from the Instituto de Salud Carlos III (MePRAM Project, PMP22/00092), and by the Study Group on Mechanisms of Action and Resistance to Antimicrobials, GEMARA (SEIMC).