The ng_zeta 1 toxin of the gonococcal epsilon/zeta toxin/antitoxin system drains precursors for cell wall synthesis

Andrea Rocker, Madeleine Peschke, Tiia Kittila, Roman Sakson, Clara Brieke, Anton Meinhart

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Bacterial toxin–antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin–antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1. Contrary to previously studied streptococcal epsilon/zeta TA systems, ng_ɛ1 has an epsilon-unrelated fold and ng_ζ1 displays broader substrate specificity and phosphorylates multiple UDP-activated sugars that are precursors of peptidoglycan and lipopolysaccharide synthesis. Moreover, the phosphorylation site is different from the streptococcal zeta toxins, resulting in a different interference with cell wall synthesis. This difference most likely reflects adaptation to the individual cell wall composition of Gram-negative and Gram-positive organisms but also the distinct involvement of cell wall components in virulence.
Original languageEnglish
Article number1686
Number of pages11
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 27 Apr 2018
Externally publishedYes

Keywords

  • enzyme mechanisms
  • pathogens
  • x-ray crystallography

Cite this

Rocker, Andrea ; Peschke, Madeleine ; Kittila, Tiia ; Sakson, Roman ; Brieke, Clara ; Meinhart, Anton. / The ng_zeta 1 toxin of the gonococcal epsilon/zeta toxin/antitoxin system drains precursors for cell wall synthesis. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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abstract = "Bacterial toxin–antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin–antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1. Contrary to previously studied streptococcal epsilon/zeta TA systems, ng_ɛ1 has an epsilon-unrelated fold and ng_ζ1 displays broader substrate specificity and phosphorylates multiple UDP-activated sugars that are precursors of peptidoglycan and lipopolysaccharide synthesis. Moreover, the phosphorylation site is different from the streptococcal zeta toxins, resulting in a different interference with cell wall synthesis. This difference most likely reflects adaptation to the individual cell wall composition of Gram-negative and Gram-positive organisms but also the distinct involvement of cell wall components in virulence.",
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The ng_zeta 1 toxin of the gonococcal epsilon/zeta toxin/antitoxin system drains precursors for cell wall synthesis. / Rocker, Andrea; Peschke, Madeleine; Kittila, Tiia; Sakson, Roman; Brieke, Clara; Meinhart, Anton.

In: Nature Communications, Vol. 9, No. 1, 1686, 27.04.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The ng_zeta 1 toxin of the gonococcal epsilon/zeta toxin/antitoxin system drains precursors for cell wall synthesis

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AU - Kittila, Tiia

AU - Sakson, Roman

AU - Brieke, Clara

AU - Meinhart, Anton

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N2 - Bacterial toxin–antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin–antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1. Contrary to previously studied streptococcal epsilon/zeta TA systems, ng_ɛ1 has an epsilon-unrelated fold and ng_ζ1 displays broader substrate specificity and phosphorylates multiple UDP-activated sugars that are precursors of peptidoglycan and lipopolysaccharide synthesis. Moreover, the phosphorylation site is different from the streptococcal zeta toxins, resulting in a different interference with cell wall synthesis. This difference most likely reflects adaptation to the individual cell wall composition of Gram-negative and Gram-positive organisms but also the distinct involvement of cell wall components in virulence.

AB - Bacterial toxin–antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin–antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1. Contrary to previously studied streptococcal epsilon/zeta TA systems, ng_ɛ1 has an epsilon-unrelated fold and ng_ζ1 displays broader substrate specificity and phosphorylates multiple UDP-activated sugars that are precursors of peptidoglycan and lipopolysaccharide synthesis. Moreover, the phosphorylation site is different from the streptococcal zeta toxins, resulting in a different interference with cell wall synthesis. This difference most likely reflects adaptation to the individual cell wall composition of Gram-negative and Gram-positive organisms but also the distinct involvement of cell wall components in virulence.

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