A Ribosomal Protein Homolog Governs Gene Expression and Virulence in a Bacterial Pathogen.

The molecular machine necessary for protein synthesis, the ribosome, is generally considered constitutively functioning and lacking any inherent regulatory capacity. Yet ribosomes are commonly heterogeneous in composition and the impact of ribosome heterogeneity on translation is not well understood. Here, we determined that changes in ribosome protein composition govern gene expression in the intracellular bacterial pathogen Francisella tularensis. F. tularensis encodes three distinct homologs for bS21, a ribosomal protein involved in translation initiation, and analysis of purified F. tularensis ribosomes revealed they are heterogeneous with respect to bS21. The loss of one homolog, bS21-2, resulted in significant changes to the cellular proteome unlinked to changes in the transcriptome. Among the reduced proteins were components of the type VI secretion system (T6SS), an essential virulence factor encoded by the Francisella Pathogenicity Island. Furthermore, loss of bS21-2 led to an intramacrophage growth defect. Although multiple bS21 homologs complemented the loss of bS21-2 with respect to T6SS protein abundance, bS21-2 was uniquely necessary for robust intramacrophage growth, suggesting bS21-2 modulates additional virulence gene(s) distinct from the T6SS. Our results indicate that ribosome composition in F. tularensis, either directly or indirectly, posttranscriptionally modulates gene expression and virulence. Our findings are consistent with a model in which bS21 homologs function as posttranscriptional regulators, allowing preferential translation of specific subsets of mRNAs, likely at the stage of translation initiation. This work also raises the possibility that bS21 in other organisms may function similarly and that ribosome heterogeneity may permit many bacteria to posttranscriptionally regulate gene expression.