Bacterial effector modifies host messenger RNA to promote virulence

ABSTRACT: Bacterial pathogens harbor specialized secretion systems that inject effector proteins into the host cell toestablish infection and disease. While many bacterial effectors post-translationally modify proteins to influencehost responses, the extent to which effectors modify host RNA is currently unknown. Here we performedRNA-interactome capture (RIC) to isolate effectors bound to host cellular messenger RNA (mRNA)during Legionella pneumophila infection. RIC identified an uncharacterized effector, FadA (Lpw16921), whichlocalized to the host-cell nucleus and interacted with host mRNAs at uracil (U)-rich RNA motifs. FadA exhibitedNADPH-oxidase activity that mediated 8-oxo-guanine (oxo8G) modifications of mRNA substrates, resultingin oxidative damage and inhibition of translation. Infection with L. pneumophila harboring wild-typeFadA, 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 secretedQ2 effector to post-transcriptionally modify host mRNA as a mechanism to promote bacterial virulence.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Cell Culture

DISEASE(S): Legionnaires' Disease

SUBMITTER: Kathleen McCaffrey  

LAB HEAD: Kathleen McCaffrey

PROVIDER: PXD070774 | Pride | 2026-08-14

REPOSITORIES: Pride