Alarmone Ap4A is elevated by aminoglycoside antibiotics and enhances their bactericidal activity.

Acid Anhydride Hydrolases / genetics Acinetobacter baumannii / genetics Anti-Bacterial Agents / pharmacology Carrier Proteins / genetics Dinucleoside Phosphates / genetics Escherichia coli / genetics Escherichia coli Proteins / genetics Kanamycin / pharmacology Pseudomonas aeruginosa / genetics
alarmone aminoglycoside antibiotic action diadenosine tetraphosphate Ap4A kanamycin

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
07 05 2019
Historique:
pubmed: 21 4 2019
medline: 17 3 2020
entrez: 21 4 2019
Statut: ppublish

Résumé

Second messenger molecules play important roles in the responses to various stimuli that can determine a cell's fate under stress conditions. Here, we report that lethal concentrations of aminoglycoside antibiotics result in the production of a dinucleotide alarmone metabolite-diadenosine tetraphosphate (Ap4A), which promotes bacterial cell killing by this class of antibiotics. We show that the treatment of

Identifiants

DOI: 10.1073/pnas.1822026116 PMID: 31004054 PMC: PMC6511005
pubmed: 31004054
pii: 1822026116
doi: 10.1073/pnas.1822026116
pmc: PMC6511005
doi:

Substances chimiques

Anti-Bacterial Agents 0
Carrier Proteins 0
Dinucleoside Phosphates 0
Escherichia coli Proteins 0
LysU protein, E coli 0
diadenosine tetraphosphate 5542-28-9
Kanamycin 59-01-8
Acid Anhydride Hydrolases EC 3.6.-
ApaH protein, E coli EC 3.6.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9578-9585

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI026289
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI018045
Pays : United States

Informations de copyright

Copyright © 2019 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Xia Ji (X)

Faculty of Health Sciences, University of Macau, Macau SAR, China.

Jin Zou (J)

Faculty of Health Sciences, University of Macau, Macau SAR, China.

Haibo Peng (H)

Faculty of Health Sciences, University of Macau, Macau SAR, China.

Anne-Sophie Stolle (AS)

Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.

Ruiqiang Xie (R)

Faculty of Health Sciences, University of Macau, Macau SAR, China.

Hongjie Zhang (H)

Faculty of Health Sciences, University of Macau, Macau SAR, China.

Bo Peng (B)

School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China.
ORCID: 0000-0002-5698-6097

John J Mekalanos (JJ)

Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; junzheng@um.edu.mo john_mekalanos@hms.harvard.edu.

Jun Zheng (J)

Faculty of Health Sciences, University of Macau, Macau SAR, China; junzheng@um.edu.mo john_mekalanos@hms.harvard.edu.
Institute of Translational Medicine, University of Macau, Macau SAR, China.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Acid anhydride hydrolases › Alarmone Ap4A is elevated by aminoglycoside...
questionsmedicales.fr › Bactéries › Proteobacteria › Gammaproteobacteria › Moraxellaceae › Acinetobacter › Acinetobacter baumannii › Alarmone Ap4A is elevated by aminoglycoside...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › Alarmone Ap4A is elevated by aminoglycoside...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Alarmone Ap4A is elevated by aminoglycoside...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Dinucléoside phosphates › Alarmone Ap4A is elevated by aminoglycoside...
questionsmedicales.fr › Bactéries › Proteobacteria › Gammaproteobacteria › Enterobacteriaceae › Escherichia › Escherichia coli › Alarmone Ap4A is elevated by aminoglycoside...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines bactériennes › Protéines Escherichia coli › Alarmone Ap4A is elevated by aminoglycoside...
questionsmedicales.fr › Glucides › Hétérosides › Aminosides › Kanamycine › Alarmone Ap4A is elevated by aminoglycoside...
questionsmedicales.fr › Bactéries › Proteobacteria › Gammaproteobacteria › Pseudomonadaceae › Pseudomonas › Pseudomonas aeruginosa › Alarmone Ap4A is elevated by aminoglycoside...