A <i>trans</i> -acting leader RNA from a <i>Salmonella</i> virulence gene

Abstract

Bacteria use flagella to move toward nutrients, find its host, or retract from toxic substances. Because bacterial flagellum is one of the ligands that activate the host innate immune system, its synthesis should be tightly regulated during host infection, which is largely unknown. Here, we report that a bacterial leader mRNA from the <i>mgtCBR</i> virulence operon in the intracellular pathogen <i>Salmonella enterica</i> serovar Typhimurium binds to the <i>fljB</i> coding region of mRNAs in the <i>fljBA</i> operon encoding the FljB phase 2 flagellin, a main component of bacterial flagella and the FljA repressor for the FliC phase 1 flagellin, and degrades <i>fljBA</i> mRNAs in an RNase E-dependent fashion during infection. A nucleotide substitution of the <i>fljB</i> flagellin gene that prevents the <i>mgtC</i> leader RNA-mediated down-regulation increases the <i>fljB</i>-encoded flagellin synthesis, leading to a hypermotile phenotype inside macrophages. Moreover, the <i>fljB</i> nucleotide substitution renders <i>Salmonella</i> hypervirulent, indicating that FljB-based motility must be compromised in the phagosomal compartment where <i>Salmonella</i> resides. This suggests that this pathogen promotes pathogenicity by producing a virulence protein and limits locomotion by a <i>trans</i>-acting leader RNA from the same virulence gene during infection.