A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>

<i>Pseudomonas aeruginosa</i> can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit...

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Autores principales:	Ahmed Al Saqr, Mohammed F. Aldawsari, El-Sayed Khafagy, Moataz A. Shaldam, Wael A. H. Hegazy, Hisham A. Abbas
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	quorum sensing allopurinol virulence inhibition <i>Pseudomonas aeruginosa</i> Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d4c4d2fcd7af4ca2aaa8edb7d474e510
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spelling	oai:doaj.org-article:d4c4d2fcd7af4ca2aaa8edb7d474e5102021-11-25T16:24:27ZA Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>10.3390/antibiotics101113852079-6382https://doaj.org/article/d4c4d2fcd7af4ca2aaa8edb7d474e5102021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1385https://doaj.org/toc/2079-6382<i>Pseudomonas aeruginosa</i> can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the <i>P. aeruginosa</i> PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled <i>Chromobacterium violaceum</i> CV026 violet pigment violacein and other <i>P. aeruginosa</i> QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of <i>P. aeruginosa</i> and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of <i>P. aeruginosa</i> infection.Ahmed Al SaqrMohammed F. AldawsariEl-Sayed KhafagyMoataz A. ShaldamWael A. H. HegazyHisham A. AbbasMDPI AGarticlequorum sensingallopurinolvirulence inhibition<i>Pseudomonas aeruginosa</i>Therapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1385, p 1385 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	quorum sensing allopurinol virulence inhibition <i>Pseudomonas aeruginosa</i> Therapeutics. Pharmacology RM1-950
spellingShingle	quorum sensing allopurinol virulence inhibition <i>Pseudomonas aeruginosa</i> Therapeutics. Pharmacology RM1-950 Ahmed Al Saqr Mohammed F. Aldawsari El-Sayed Khafagy Moataz A. Shaldam Wael A. H. Hegazy Hisham A. Abbas A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>
description	<i>Pseudomonas aeruginosa</i> can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the <i>P. aeruginosa</i> PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled <i>Chromobacterium violaceum</i> CV026 violet pigment violacein and other <i>P. aeruginosa</i> QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of <i>P. aeruginosa</i> and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of <i>P. aeruginosa</i> infection.
format	article
author	Ahmed Al Saqr Mohammed F. Aldawsari El-Sayed Khafagy Moataz A. Shaldam Wael A. H. Hegazy Hisham A. Abbas
author_facet	Ahmed Al Saqr Mohammed F. Aldawsari El-Sayed Khafagy Moataz A. Shaldam Wael A. H. Hegazy Hisham A. Abbas
author_sort	Ahmed Al Saqr
title	A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>
title_short	A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>
title_full	A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>
title_fullStr	A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>
title_full_unstemmed	A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>
title_sort	novel use of allopurinol as a quorum-sensing inhibitor in <i>pseudomonas aeruginosa</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d4c4d2fcd7af4ca2aaa8edb7d474e510
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A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in <i>Pseudomonas aeruginosa</i>

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