Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters

Abstract Persisters are a sub-population of genetically sensitive bacteria that survive antibiotic treatment by entering a dormant state. The emergence of persisters from dormancy after antibiotic withdrawal leads to recurrent infection. Indole is an aromatic molecule with diverse signalling roles,...

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Autores principales:	Ashraf Zarkan, Marta Matuszewska, Stephen B. Trigg, Meng Zhang, Daaniyah Belgami, Cameron Croft, Junyan Liu, Sawssen El-Ouisi, Jack Greenhalgh, James S. Duboff, Taufiq Rahman, David K. Summers
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/199fed1a3da64621a877189cfbb04dfd
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spelling	oai:doaj.org-article:199fed1a3da64621a877189cfbb04dfd2021-12-02T15:33:12ZInhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters10.1038/s41598-020-68693-w2045-2322https://doaj.org/article/199fed1a3da64621a877189cfbb04dfd2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68693-whttps://doaj.org/toc/2045-2322Abstract Persisters are a sub-population of genetically sensitive bacteria that survive antibiotic treatment by entering a dormant state. The emergence of persisters from dormancy after antibiotic withdrawal leads to recurrent infection. Indole is an aromatic molecule with diverse signalling roles, including a role in persister formation. Here we demonstrate that indole stimulates the formation of Escherichia coli persisters against quinolone antibiotics which target the GyrA subunit of DNA gyrase. However, indole has no effect on the formation of E. coli persisters against an aminocoumarin, novobiocin, which targets the GyrB subunit of DNA gyrase. Two modes of indole signalling have been described: persistent and pulse. The latter refers to the brief but intense elevation of intracellular indole during stationary phase entry. We show that the stimulation of quinolone persisters is due to indole pulse, rather than persistent, signalling. In silico docking of indole on DNA gyrase predicts that indole docks perfectly to the ATP binding site of the GyrB subunit. We propose that the inhibition of indole production offers a potential route to enhance the activity of quinolones against E. coli persisters.Ashraf ZarkanMarta MatuszewskaStephen B. TriggMeng ZhangDaaniyah BelgamiCameron CroftJunyan LiuSawssen El-OuisiJack GreenhalghJames S. DuboffTaufiq RahmanDavid K. SummersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ashraf Zarkan Marta Matuszewska Stephen B. Trigg Meng Zhang Daaniyah Belgami Cameron Croft Junyan Liu Sawssen El-Ouisi Jack Greenhalgh James S. Duboff Taufiq Rahman David K. Summers Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters
description	Abstract Persisters are a sub-population of genetically sensitive bacteria that survive antibiotic treatment by entering a dormant state. The emergence of persisters from dormancy after antibiotic withdrawal leads to recurrent infection. Indole is an aromatic molecule with diverse signalling roles, including a role in persister formation. Here we demonstrate that indole stimulates the formation of Escherichia coli persisters against quinolone antibiotics which target the GyrA subunit of DNA gyrase. However, indole has no effect on the formation of E. coli persisters against an aminocoumarin, novobiocin, which targets the GyrB subunit of DNA gyrase. Two modes of indole signalling have been described: persistent and pulse. The latter refers to the brief but intense elevation of intracellular indole during stationary phase entry. We show that the stimulation of quinolone persisters is due to indole pulse, rather than persistent, signalling. In silico docking of indole on DNA gyrase predicts that indole docks perfectly to the ATP binding site of the GyrB subunit. We propose that the inhibition of indole production offers a potential route to enhance the activity of quinolones against E. coli persisters.
format	article
author	Ashraf Zarkan Marta Matuszewska Stephen B. Trigg Meng Zhang Daaniyah Belgami Cameron Croft Junyan Liu Sawssen El-Ouisi Jack Greenhalgh James S. Duboff Taufiq Rahman David K. Summers
author_facet	Ashraf Zarkan Marta Matuszewska Stephen B. Trigg Meng Zhang Daaniyah Belgami Cameron Croft Junyan Liu Sawssen El-Ouisi Jack Greenhalgh James S. Duboff Taufiq Rahman David K. Summers
author_sort	Ashraf Zarkan
title	Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters
title_short	Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters
title_full	Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters
title_fullStr	Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters
title_full_unstemmed	Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters
title_sort	inhibition of indole production increases the activity of quinolone antibiotics against e. coli persisters
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/199fed1a3da64621a877189cfbb04dfd
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Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters

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