Bacterial effector modifies host messenger RNA to promote virulence

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.