Header

UZH-Logo

Maintenance Infos

Gallium-mediated siderophore quenching as an evolutionarily robust antibacterial treatment


Ross-Gillespie, Adin; Weigert, M; Brown, S P; Kümmerli, Rolf (2014). Gallium-mediated siderophore quenching as an evolutionarily robust antibacterial treatment. Evolution, Medicine, and Public Health, 2014(1):18-29.

Abstract

Background and objectives: Conventional antibiotics select strongly for resistance and are consequently losing efficacy worldwide. Extracellular quenching of shared virulence factors could represent a more promising strategy because (a) it reduces the available routes to resistance (since extracellular action precludes any mutations blocking a drug’s entry into cells or hastening its exit) and (b) it weakens selection for resistance, since fitness benefits to emergent mutants are diluted across all cells in a cooperative collective. Here, we tested this hypothesis empirically.
Methodology: We used gallium to quench the iron-scavenging siderophores secreted and shared among pathogenic Pseudomonas aeruginosa bacteria, and quantitatively monitored its effects on growth in vitro. We assayed virulence in acute infections of caterpillar hosts (Galleria mellonella), and tracked resistance emergence over time using experimental evolution.
Results: Gallium strongly inhibited bacterial growth in vitro, primarily via its siderophore quenching activity. Moreover, bacterial siderophore production peaked at intermediate gallium concentrations, indicating additional metabolic costs in this range. In vivo, gallium attenuated virulence and growth – even more so than in infections with siderophore-deficient strains. Crucially, while resistance soon evolved against conventional antibiotic treatments, gallium treatments retained their efficacy over time.

Abstract

Background and objectives: Conventional antibiotics select strongly for resistance and are consequently losing efficacy worldwide. Extracellular quenching of shared virulence factors could represent a more promising strategy because (a) it reduces the available routes to resistance (since extracellular action precludes any mutations blocking a drug’s entry into cells or hastening its exit) and (b) it weakens selection for resistance, since fitness benefits to emergent mutants are diluted across all cells in a cooperative collective. Here, we tested this hypothesis empirically.
Methodology: We used gallium to quench the iron-scavenging siderophores secreted and shared among pathogenic Pseudomonas aeruginosa bacteria, and quantitatively monitored its effects on growth in vitro. We assayed virulence in acute infections of caterpillar hosts (Galleria mellonella), and tracked resistance emergence over time using experimental evolution.
Results: Gallium strongly inhibited bacterial growth in vitro, primarily via its siderophore quenching activity. Moreover, bacterial siderophore production peaked at intermediate gallium concentrations, indicating additional metabolic costs in this range. In vivo, gallium attenuated virulence and growth – even more so than in infections with siderophore-deficient strains. Crucially, while resistance soon evolved against conventional antibiotic treatments, gallium treatments retained their efficacy over time.

Statistics

Altmetrics

Downloads

14 downloads since deposited on 05 Feb 2015
7 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Plant and Microbial Biology
Dewey Decimal Classification:580 Plants (Botany)
Language:English
Date:2014
Deposited On:05 Feb 2015 15:36
Last Modified:08 Dec 2017 10:14
Publisher:Oxford University Press
ISSN:2050-6201
Publisher DOI:https://doi.org/10.1093/emph/eou003
Official URL:http://emph.oxfordjournals.org/content/2014/1/18.full.pdf+html

Download

Download PDF  'Gallium-mediated siderophore quenching as an evolutionarily robust antibacterial treatment'.
Preview
Content: Published Version
Filetype: PDF
Size: 719kB
View at publisher
Licence: Creative Commons: Attribution 3.0 Unported (CC BY 3.0)