An ADP-ribosyltransferase toxin kills bacterial cells by modifying structured non-coding RNAs.

ADP Ribose Transferases / chemistry Adenosine Diphosphate / metabolism Anti-Bacterial Agents / metabolism Bacteria / genetics Diphtheria Toxin / genetics RNA, Catalytic / genetics RNA, Double-Stranded / metabolism Ribonuclease P / genetics Type VI Secretion Systems / metabolism Virulence Factors / metabolism
ADP-ribosyltransferases Pseudomonas aeruginosa RNA modification bacterial competition bacterial toxins mechanistic enzymology protein secretion type VI secretion systems

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
15 09 2022
Historique:
received: 23 05 2022
revised: 25 07 2022
accepted: 11 08 2022
pubmed: 8 9 2022
medline: 21 9 2022
entrez: 7 9 2022
Statut: ppublish

Résumé

ADP-ribosyltransferases (ARTs) were among the first identified bacterial virulence factors. Canonical ART toxins are delivered into host cells where they modify essential proteins, thereby inactivating cellular processes and promoting pathogenesis. Our understanding of ARTs has since expanded beyond protein-targeting toxins to include antibiotic inactivation and DNA damage repair. Here, we report the discovery of RhsP2 as an ART toxin delivered between competing bacteria by a type VI secretion system of Pseudomonas aeruginosa. A structure of RhsP2 reveals that it resembles protein-targeting ARTs such as diphtheria toxin. Remarkably, however, RhsP2 ADP-ribosylates 2'-hydroxyl groups of double-stranded RNA, and thus, its activity is highly promiscuous with identified cellular targets including the tRNA pool and the RNA-processing ribozyme, ribonuclease P. Consequently, cell death arises from the inhibition of translation and disruption of tRNA processing. Overall, our data demonstrate a previously undescribed mechanism of bacterial antagonism and uncover an unprecedented activity catalyzed by ART enzymes.

Identifiants

DOI: 10.1016/j.molcel.2022.08.015 PMID: 36070765
pubmed: 36070765
pii: S1097-2765(22)00804-8
doi: 10.1016/j.molcel.2022.08.015
pii:
doi:

Substances chimiques

Anti-Bacterial Agents 0
Diphtheria Toxin 0
RNA, Catalytic 0
RNA, Double-Stranded 0
Type VI Secretion Systems 0
Virulence Factors 0
Adenosine Diphosphate 61D2G4IYVH
ADP Ribose Transferases EC 2.4.2.-
Ribonuclease P EC 3.1.26.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3484-3498.e11

Subventions

Organisme : CIHR
ID : PJT-175011
Pays : Canada
Organisme : Medical Research Council
ID : MR/N023250/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S02316X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N002539/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K001930/1
Pays : United Kingdom

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Nathan P Bullen (NP)

Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.

David Sychantha (D)

Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.

Stephanie S Thang (SS)

Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.

Peter H Culviner (PH)

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Marta Rudzite (M)

MRC Centre for Molecular Bacteriology and Infection (CMBI), Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

Shehryar Ahmad (S)

Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.

Vraj S Shah (VS)

Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.

Alain Filloux (A)

MRC Centre for Molecular Bacteriology and Infection (CMBI), Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

Gerd Prehna (G)

Department of Microbiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.

John C Whitney (JC)

Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada; David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address: jwhitney@mcmaster.ca.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Glycosyltransferase › Pentosyltransferases › ADP ribose transferases › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › ADP › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Bactéries › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Toxine diphtérique › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › ARN catalytique › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › ARN double brin › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Ribonucléoprotéines › Ribonuclease P › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Structures macromoléculaires › Complexes multiprotéiques › Systèmes de translocation des protéines › Systèmes bactériens de sécrétion › Systèmes de sécrétion de type VI › An ADP-ribosyltransferase toxin kills...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Facteurs de virulence › An ADP-ribosyltransferase toxin kills...