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Thus far, ribosome hibernation factors of\n                      <jats:italic toggle=\"yes\">L. pneumophila<\/jats:italic>\n                      have not been characterized. Here, we show that\n                      <jats:italic toggle=\"yes\">L. pneumophila<\/jats:italic>\n                      encodes homologs of the ribosome hibernating factors LhpF (Lpg1206), RaiA (Lpg0467), RsfS (Lpg1377), and the GTPase HflX (Lpg0010), which define the ribosome populations by mediating 100S ribosome dimerization, 70S inactivation, ribosome assembly inhibition, and ribosome splitting, respectively. Exceptional among \u03b3-proteobacteria,\n                      <jats:italic toggle=\"yes\">L. pneumophila<\/jats:italic>\n                      forms 100S ribosome dimers during exponential growth. Functional studies show that the hibernation factors support survival upon starvation, regrowth, efficient host infection, and virulence factor production of\n                      <jats:italic toggle=\"yes\">L. pneumophila<\/jats:italic>\n                      . Furthermore, they enhance antibiotic tolerance and shape intracellular heterogeneity of bacterial growth and motility. Our findings identify ribosome hibernation as a central mechanism by which\n                      <jats:italic toggle=\"yes\">L. pneumophila<\/jats:italic>\n                      orchestrates survival, persistence, and infection, highlighting its critical role in bacterial physiology and pathogenesis.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Due to nutrient limitation and adverse conditions in the environment, bacteria mostly do not grow exponentially but adopt a resting (\u201cdormant\u201d) state. Bacterial dormancy usually coincides with the formation of translationally silent (\u201chibernating\u201d) ribosomes; however, the role of ribosome hibernation in intracellular pathogens is poorly understood. The facultative intracellular bacterium\n                        <jats:italic toggle=\"yes\">Legionella pneumophila<\/jats:italic>\n                        is virulent in the stationary but not in the exponential growth phase, and therefore, an in-depth characterization of the pathogen\u2019s physiological states and ribosome profiles is crucial for understanding its virulence. Using bioinformatics, bacterial genetics, biochemical, and cell biological approaches, in this study, we reveal that the\n                        <jats:italic toggle=\"yes\">L. pneumophila<\/jats:italic>\n                        ribosome hibernation factors LhpF, RaiA, RsfS, and HflX determine distinct ribosome subpopulations and are implicated in starvation survival and regrowth, as well as in host cell infection, intracellular replication, and phenotypic heterogeneity. Collectively, our data highlight the critical importance of ribosome hibernation for the physiology and virulence of\n                        <jats:italic toggle=\"yes\">L. pneumophila<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03762-25","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:00:33Z","timestamp":1769781633000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Regulation of ribosome hibernation controls\n                    <i>Legionella<\/i>\n                    survival, infection, antibiotic tolerance, and phenotypic heterogeneity"],"prefix":"10.1128","volume":"17","author":[{"given":"Camille","family":"Schmid","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University of Z\u00fcrich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina Natalie","family":"Trinkler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University of Z\u00fcrich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth Teresa","family":"Vittori","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology, University of Z\u00fcrich","place":["Z\u00fcrich, 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