Activation of contact-dependent antibacterial tRNase toxins by translation elongation factors.

Abstract:

:Contact-dependent growth inhibition (CDI) is a mechanism by which bacteria exchange toxins via direct cell-to-cell contact. CDI systems are distributed widely among Gram-negative pathogens and are thought to mediate interstrain competition. Here, we describe tsf mutations that alter the coiled-coil domain of elongation factor Ts (EF-Ts) and confer resistance to the CdiA-CTEC869 tRNase toxin from enterohemorrhagic Escherichia coli EC869. Although EF-Ts is required for toxicity in vivo, our results indicate that it is dispensable for tRNase activity in vitro. We find that CdiA-CTEC869 binds to elongation factor Tu (EF-Tu) with high affinity and this interaction is critical for nuclease activity. Moreover, in vitro tRNase activity is GTP-dependent, suggesting that CdiA-CTEC869 only cleaves tRNA in the context of translationally active GTP·EF-Tu·tRNA ternary complexes. We propose that EF-Ts promotes the formation of GTP·EF-Tu·tRNA ternary complexes, thereby accelerating substrate turnover for rapid depletion of target-cell tRNA.

authors

Jones AM,Garza-Sánchez F,So J,Hayes CS,Low DA

doi

10.1073/pnas.1619273114

subject

Has Abstract

pub_date

2017-03-07 00:00:00

pages

E1951-E1957

issue

10

eissn

0027-8424

issn

1091-6490

pii

1619273114

journal_volume

114

pub_type

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