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

Published version
Peer-reviewed

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Authors

Zarkan, Ashraf 
Matuszewska, Marta 
Trigg, Stephen B. 
Zhang, Meng 
Belgami, Daaniyah 

Abstract

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.

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Keywords

Article, /631/326/22, /631/326/1320, article

Journal Title

Scientific Reports

Conference Name

Journal ISSN

2045-2322

Volume Title

10

Publisher

Nature Publishing Group UK
Sponsorship
Leverhulme Trust (RPG-2015-184)
Innovate UK (SBRI 971621)
Wellcome Trust Developing Concept Fund (RG93172)
Medical Research Council (Research Studentship)
Biotechnology and Biological Sciences Research Council (Research Studentship)
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