Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence - PubMed (original) (raw)

Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence

Jintae Lee et al. Microb Biotechnol. 2009 Jan.

Abstract

Indole is an extracellular biofilm signal for Escherichia coli, and many bacterial oxygenases readily convert indole to various oxidized compounds including 7-hydroxyindole (7HI). Here we investigate the impact of indole and 7HI on Pseudomonas aeruginosa PAO1 virulence and quorum sensing (QS)-regulated phenotypes; this strain does not synthesize these compounds but degrades them rapidly. Indole and 7HI both altered extensively gene expression in a manner opposite that of acylhomoserine lactones; the most repressed genes encode the mexGHI-opmD multidrug efflux pump and genes involved in the synthesis of QS-regulated virulence factors including pyocyanin (phz operon), 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) signal (pqs operon), pyochelin (pch operon) and pyoverdine (pvd operon). Corroborating these microarray results, indole and 7HI decreased production of pyocyanin, rhamnolipid, PQS and pyoverdine and enhanced antibiotic resistance. In addition, indole affected the utilization of carbon, nitrogen and phosphorus, and 7HI abolished swarming motility. Furthermore, 7HI reduced pulmonary colonization of P. aeruginosa in guinea pigs and increased clearance in lungs. Hence, indole-related compounds have potential as a novel antivirulence approach for the recalcitrant pathogen P. aeruginosa.

© 2008 The Authors; Journal compilation © 2008 Society for Applied Microbiology and Blackwell Publishing Ltd.

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Figures

Figure 1

Figure 1

Reduction of virulence factors by indole and 7HI. Production of virulence factors with 1.0 mM indole, 0.5 mM 7HI and 1.0 mM IAA (negative control) with P. aeruginosa PAO1 (A), with P. aeruginosa PAO1 mexI (B) and P. aeruginosa PAO1 mvfR (C). For clarity, wild‐type values are not shown in (B) and (C) so bars indicate the relative amount of each compound made compared with the wild‐type strain without indole or 7HI added. Each experiment was performed with at least two independent cultures. Data show the average of the replicates, and one standard deviation is shown.

Figure 2

Figure 2

Inhibition of swarming motility by indole and 7HI. Swarming motility of P. aeruginosa on BM2 medium with 0.5% agar with 1.0 mM indole and 0.5 mM 7HI after 28 h. Each experiment was performed with at least two independent cultures and one representative data set is shown.

Figure 3

Figure 3

Degradation of indole and 7HI by P. aeruginosa. Pseudomonas aeruginosa degrades 0.5 mM indole (A) and 0.5 mM 7HI (B) in LB. The initial turbidity of cells was 1.0 at 600 nm. Closed square data (▪) are from live cells, open square data (□) are from autoclaved cells (dead cell control) and open circle data (○) are from live cells that lack added indole or 7HI. Each experiment was performed using two independent cultures, and one representative data set is shown.

Figure 4

Figure 4

Reduction of virulence of P. aeruginosa in guinea pigs. A. Colonization and clearance of P. aeruginosa pre‐treated with 7HI or solvent (DMF) prior to infection of guinea pigs by aerosol with ∼2 × 105 cfu. Average of five replicates, and one standard deviation is shown. B. Real‐time analysis of P. aeruginosa pre‐treated with 7HI or solvent (DMF) in the acute guinea pig infection model (representative guinea pigs are shown for each group and are imaged laterally) using the Xenogen IVIS CCD camera. Colour bar represents the intensity of luminescent signal in photons s−1 cm−2 from low (blue) to high (red).

Figure 5

Figure 5

Summary of indole‐affected processes in _P. aeruginosa_→ indicates induction of gene expression or stimulation of a phenotype, ? indicates repression of gene expression or repression of a phenotype, and black arrows indicate reactions.

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