The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth

Carbonic anhydrases, catalysing the reversible CO2 hydration reaction, contribute in all living organisms to the maintenance of stable metabolic functions depending on intracellular concentrations of carbon dioxide, bicarbonate, and protons. Recent studies have examined how CAs affect bacterial life...

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Main Authors: Viviana De Luca, Vincenzo Carginale, Claudiu T. Supuran, Clemente Capasso
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
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Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2022.2101644
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author Viviana De Luca
Vincenzo Carginale
Claudiu T. Supuran
Clemente Capasso
author_facet Viviana De Luca
Vincenzo Carginale
Claudiu T. Supuran
Clemente Capasso
author_sort Viviana De Luca
collection DOAJ
description Carbonic anhydrases, catalysing the reversible CO2 hydration reaction, contribute in all living organisms to the maintenance of stable metabolic functions depending on intracellular concentrations of carbon dioxide, bicarbonate, and protons. Recent studies have examined how CAs affect bacterial lifecycle, considering these enzymes druggable targets due to interference with their activities by using inhibitors or activators. Here, we propose Escherichia coli cells as a model for testing the effect of acetazolamide (AZA), a potent CA inhibitor, on bacterial survival by evaluating E. coli growth through its glucose consumption. AZA, at concentrations higher than 31.2 µg/mL, was able to impair E. coli growth and glucose uptake. AZA is a good inhibitor of the two recombinant E. coli CAs, the β-CA CynT2, and the γ-CA EcoCAγ, with KIs of 227 and 248 nM, respectively. This study provides a proof-of-concept, low-cost method for identifying effective CA inhibitors capable of impairing bacterial metabolism.
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1475-6374
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publishDate 2022-12-01
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series Journal of Enzyme Inhibition and Medicinal Chemistry
spelling doaj-art-c24a82beb06d4e3fbdd07d88c98bb8a82025-08-20T02:36:30ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712092209810.1080/14756366.2022.2101644The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growthViviana De Luca0Vincenzo Carginale1Claudiu T. Supuran2Clemente Capasso3Institute of Biosciences and Bioresources, National Research Council, Napoli, ItalyInstitute of Biosciences and Bioresources, National Research Council, Napoli, ItalySection of Pharmaceutical and Nutraceutical Sciences, Department of Neurofarba, University of Florence, Florence, ItalyInstitute of Biosciences and Bioresources, National Research Council, Napoli, ItalyCarbonic anhydrases, catalysing the reversible CO2 hydration reaction, contribute in all living organisms to the maintenance of stable metabolic functions depending on intracellular concentrations of carbon dioxide, bicarbonate, and protons. Recent studies have examined how CAs affect bacterial lifecycle, considering these enzymes druggable targets due to interference with their activities by using inhibitors or activators. Here, we propose Escherichia coli cells as a model for testing the effect of acetazolamide (AZA), a potent CA inhibitor, on bacterial survival by evaluating E. coli growth through its glucose consumption. AZA, at concentrations higher than 31.2 µg/mL, was able to impair E. coli growth and glucose uptake. AZA is a good inhibitor of the two recombinant E. coli CAs, the β-CA CynT2, and the γ-CA EcoCAγ, with KIs of 227 and 248 nM, respectively. This study provides a proof-of-concept, low-cost method for identifying effective CA inhibitors capable of impairing bacterial metabolism.https://www.tandfonline.com/doi/10.1080/14756366.2022.2101644Carbonic anhydrasessulphonamideinhibitorphenol-sulphuric acid assayglucose consumptionbacterial growth
spellingShingle Viviana De Luca
Vincenzo Carginale
Claudiu T. Supuran
Clemente Capasso
The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth
Journal of Enzyme Inhibition and Medicinal Chemistry
Carbonic anhydrases
sulphonamide
inhibitor
phenol-sulphuric acid assay
glucose consumption
bacterial growth
title The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth
title_full The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth
title_fullStr The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth
title_full_unstemmed The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth
title_short The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth
title_sort gram negative bacterium escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth
topic Carbonic anhydrases
sulphonamide
inhibitor
phenol-sulphuric acid assay
glucose consumption
bacterial growth
url https://www.tandfonline.com/doi/10.1080/14756366.2022.2101644
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