Nitric oxide disrupts bacterial cytokinesis by poisoning purine metabolism

Jessica Jones-Carson; Atsushi Yahashiri; Ju-Sim Kim; Lin Liu; Liam F Fitzsimmons; David S Weiss; Andrés Vázquez-Torres

doi:10.1126/sciadv.aaz0260

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Nitric oxide disrupts bacterial cytokinesis by poisoning purine metabolism

Journal article

Open access

Peer reviewed

Nitric oxide disrupts bacterial cytokinesis by poisoning purine metabolism

Jessica Jones-Carson, Atsushi Yahashiri, Ju-Sim Kim, Lin Liu, Liam F Fitzsimmons, David S Weiss and Andrés Vázquez-Torres

Science advances, Vol.6(9), pp.eaaz0260-eaaz0260

02/2020

DOI: 10.1126/sciadv.aaz0260

PMCID: PMC7043908

PMID: 32133408

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Abstract

Cytostasis is the most salient manifestation of the potent antimicrobial activity of nitric oxide (NO), yet the mechanism by which NO disrupts bacterial cell division is unknown. Here, we show that in respiring , and , NO arrests the first step in division, namely, the GTP-dependent assembly of the bacterial tubulin homolog FtsZ into a cytokinetic ring. FtsZ assembly fails in respiring cells because NO inactivates inosine 5'-monophosphate dehydrogenase in de novo purine nucleotide biosynthesis and quinol oxidases in the electron transport chain, leading to drastic depletion of nucleoside triphosphates, including the GTP needed for the polymerization of FtsZ. Despite inhibiting respiration and dissipating proton motive force, NO does not destroy Z ring formation and only modestly decreases nucleoside triphosphates in glycolytic cells, which obtain much of their ATP by substrate-level phosphorylation and overexpress inosine 5'-monophosphate dehydrogenase. Purine metabolism dictates the susceptibility of early morphogenic steps in cytokinesis to NO toxicity.

Bacillus subtilis - genetics

Bacillus subtilis - metabolism

Bacterial Proteins - genetics

Bacterial Proteins - metabolism

Cytokinesis - drug effects

Cytokinesis - genetics

Cytoskeletal Proteins - genetics

Cytoskeletal Proteins - metabolism

Escherichia coli - genetics

Escherichia coli - metabolism

Nitric Oxide - pharmacology

Oxygen Consumption - drug effects

Oxygen Consumption - genetics

Proton-Motive Force - drug effects

Proton-Motive Force - genetics

Salmonella - genetics

Salmonella - metabolism

Details

Title: Subtitle: Nitric oxide disrupts bacterial cytokinesis by poisoning purine metabolism
Creators: Jessica Jones-Carson - University of Colorado Denver
Atsushi Yahashiri - University of Iowa
Ju-Sim Kim - University of Colorado Denver
Lin Liu - University of Colorado Denver
Liam F Fitzsimmons - University of Colorado Denver
David S Weiss - Roy J. and Lucille A. Carver College of Medicine
Andrés Vázquez-Torres - University of Colorado Denver
Resource Type: Journal article
Publication Details: Science advances, Vol.6(9), pp.eaaz0260-eaaz0260
DOI: 10.1126/sciadv.aaz0260
PMID: 32133408
PMCID: PMC7043908
ISSN: 2375-2548
eISSN: 2375-2548
Grant note: F31 AI118223 / NIAID NIH HHS T32 AI052066 / NIAID NIH HHS R01 GM125656 / NIGMS NIH HHS R01 AI054959 / NIAID NIH HHS R01 AI136520 / NIAID NIH HHS R01 DA036520 / NIDA NIH HHS F32 AI010181 / NIAID NIH HHS
Language: English
Date published: 02/2020
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297326202771

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