tRNA queuosine modification is involved in biofilm formation and virulence in bacteria

Abstract tRNA modifications are crucial for fine-tuning of protein translation. Queuosine (Q) modification of tRNAs is thought to modulate the translation rate of NAU codons, but its physiological role remains elusive. Therefore, we hypothesize that Q-tRNAs control those physiological processes involving NAU codon-enriched genes (Q-genes). Here, we report a novel bioinformatic strategy to predict Q-genes, revealing a widespread enrichment in functions, especially those related to biofilm formation and virulence in bacteria, and particularly in human pathogens. Indeed, we experimentally verified that these processes were significantly affected by altering the degree of tRNA Q-modification in different model bacteria, representing the first report of a general mechanism controlling biofilm formation and virulence in Gram-positive and Gram-negative bacteria possibly through the coordination of the expression of functionally related genes. Furthermore, we propose that changes in Q availability in a microbiome would affect its functionality. Our findings open the door to the control of bacterial infections and biofilm formation by inhibition of tRNA Q-modification. Graphical Abstract Graphical Abstract