Bacterial effector modifies host messenger RNA to promote virulence

Bacterial pathogens harbor specialized secretion systems that inject effector proteins into the host cell to establish infection and disease. While many bacterial effectors post-translationally modify proteins to influence host responses, the extent to which effectors modify host RNA is currently unknown. Here we performed RNA-interactome capture (RIC) to isolate effectors bound to host cellular messenger RNA (mRNA) during Legionella pneumophila infection. RIC identified an uncharacterized effector, FadA (Lpw16921), which localized to the host-cell nucleus and interacted with host mRNAs at uracil (U)-rich RNA motifs. FadA exhibited NADPH-oxidase activity that mediated 8-oxo-guanine (oxo⁸G) modifications of mRNA substrates, resulting in oxidative damage and inhibition of translation. Infection with L. pneumophila harboring wild-type FadA, but not a catalytically inactive mutant, increased oxo⁸G modifications, suppressed cytokine responses, and promoted bacterial persistence in vivo. Our findings demonstrate the potential for a secreted effector to post-transcriptionally modify host mRNA as a mechanism to promote bacterial virulence.