An Interbacterial NAD(P)+ Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells

Whitney, John C.; Quentin, Dennis; Sawai, Shin; LeRoux, Michele; Harding, Brittany N.; Ledvina, Hannah E.; Tran, Bao; Robinson, Howard; Goo, Young Ah; Goodlett, David R.; Raunser, Stefan; Mougous, Joseph D.

doi:10.1016/j.cell.2015.09.027

Cited by 203 publications

(273 citation statements)

References 47 publications

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“…Unlike the CdiA-CT EC869 toxin, EF-Tu is not required for the enzymatic activity of Tse6. However, Tse6 mutations that block EF-Tu binding also abrogate the ability to intoxicate target bacteria, suggesting that the interaction with EF-Tu could be required for T6SS-mediated secretion of Tse6 or entry of the effector into the target-cell cytoplasm (37). These observations, together with the data presented herein, show that diverse bacterial toxin domains exploit EF-Tu to promote interbacterial competition.…”

Section: Discussionsupporting

confidence: 65%

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

Jones

Garza-Sánchez

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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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-CT EC869 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-CT EC869 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-CT EC869 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.cell communication | protein synthesis | toxin-immunity proteins | ribonuclease | bacterial competition

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Section: Discussionsupporting

confidence: 65%

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

Jones

Garza-Sánchez

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…9). Alternatively, as was recently described for contact-dependent inhibition (CDI) and type VI secretion (5,33), OmrA may serve as a receptor to facilitate toxin delivery across the cytoplasmic membrane. Another clue in support of a toxin-mediated interaction is the filamentation response of susceptible cells.…”

Section: Discussionmentioning

confidence: 99%

Sibling Rivalry in Myxococcus xanthus Is Mediated by Kin Recognition and a Polyploid Prophage

et al. 2016

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Myxobacteria form complex social communities that elicit multicellular behaviors. One such behavior is kin recognition, in which cells identify siblings via their polymorphic TraA cell surface receptor, to transiently fuse outer membranes and exchange their contents. In addition, outer membrane exchange (OME) regulates behaviors, such as inhibition of wild-type Myxococcus xanthus (DK1622) from swarming. Here we monitored the fate of motile cells and surprisingly found they were killed by nonmotile siblings. The kill phenotype required OME (i.e., was TraA dependent). The genetic basis of killing was traced to ancestral strains used to construct DK1622. Specifically, the kill phenotype mapped to a large "polyploid prophage," Mx alpha. Sensitive strains contained a 200-kb deletion that removed two of three Mx alpha units. To explain these results, we suggest that Mx alpha expresses a toxin-antitoxin cassette that uses the OME machinery of M. xanthus to transfer a toxin that makes the population "addicted" to Mx alpha. Thus, siblings that lost Mx alpha units (no immunity) are killed by cells that harbor the element. To test this, an Mx alpha-harboring laboratory strain was engineered (by traA allele swap) to recognize a closely related species, Myxococcus fulvus. As a result, M. fulvus, which lacks Mx alpha, was killed. These TraA-mediated antagonisms provide an explanation for how kin recognition specificity might have evolved in myxobacteria. That is, recognition specificity is determined by polymorphisms in traA, which we hypothesize were selected for because OME with non-kin leads to lethal outcomes. IMPORTANCEThe transition from single cell to multicellular life is considered a major evolutionary event. Myxobacteria have successfully made this transition. For example, in response to starvation, individual cells aggregate into multicellular fruiting bodies wherein cells differentiate into spores. To build fruits, cells need to recognize their siblings, and in part, this is mediated by the TraA cell surface receptor. Surprisingly, we report that TraA recognition can also involve sibling killing. We show that killing originates from a prophage-like element that has apparently hijacked the TraA system to deliver a toxin to kin. We hypothesize that this killing system has imposed selective pressures on kin recognition, which in turn has resulted in TraA polymorphisms and hence many different recognition groups.

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“…In one case, the T6SS toxin Tse6, produced by P. aeruginosa, contains transmembrane domains that are shielded from the aqueous environment by an associated chaperone. The chaperone, EagT6, protects Tse6 until delivery into the target's periplasm (124). This example appears to be the exception, where the majority of membrane-associated effectors lack a chaperone or other clear vectoring mechanism.…”

Section: Contact-mediated Competitionmentioning

confidence: 99%

Multifaceted Interfaces of Bacterial Competition

2016

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bMicrobial communities span many orders of magnitude, ranging in scale from hundreds of cells on a single particle of soil to billions of cells within the lumen of the gastrointestinal tract. Bacterial cells in all habitats are members of densely populated local environments that facilitate competition between neighboring cells. Accordingly, bacteria require dynamic systems to respond to the competitive challenges and the fluctuations in environmental circumstances that tax their fitness. The assemblage of bacteria into communities provides an environment where competitive mechanisms are developed into new strategies for survival. In this minireview, we highlight a number of mechanisms used by bacteria to compete between species. We focus on recent discoveries that illustrate the dynamic and multifaceted functions used in bacterial competition and discuss how specific mechanisms provide a foundation for understanding bacterial community development and function.

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An Interbacterial NAD(P)+ Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells

Cited by 203 publications

References 47 publications

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

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

Sibling Rivalry in Myxococcus xanthus Is Mediated by Kin Recognition and a Polyploid Prophage

Multifaceted Interfaces of Bacterial Competition

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