Indole inhibition of N-acylated homoserine lactone-mediated quorum signalling is widespread in Gram-negative bacteria

Abstract

The LuxI/R quorum-sensing system and its associated N-acylated homoserine lactone (AHL) signal is widespread among Gram-negative bacteria. Although inhibition by indole of AHL quorum signalling in Pseudomonas aeruginosa and Acinetobacter oleivorans has been reported previously, it has not been documented among other species. Here, we show that co-culture with wild-type Escherichia coli, but not with E. coli tnaA mutants that lack tryptophanase and as a result do not produce indole, inhibits AHL-regulated pigmentation in Chromobacterium violaceum (violacein), Pseudomonas chlororaphis (phenazine) and Serratia marcescens (prodigiosin). Loss of pigmentation also occurred during pure culture growth of Chro. violaceum, P. chlororaphis and S. marcescens in the presence of physiologically relevant indole concentrations (0.5-1.0 mM). Inhibition of violacein production by indole was counteracted by the addition of the Chro. violaceum cognate autoinducer, N-decanoyl homoserine lactone (C10-HSL), in a dosedependent manner. The addition of exogenous indole or co-culture with E. coli also affected Chro. violaceum transcription of vioA (violacein pigment production) and chiA (chitinase production), but had no effect on pykF (pyruvate kinase), which is not quorum regulated. Chro. violaceum AHL-regulated elastase and chitinase activity were inhibited by indole, as was motility. Growth of Chro. violaceum was not affected by indole or C10-HSL supplementation. Using a nematodefeeding virulence assay, we observed that survival of Caenorhabditis elegans exposed to Chro. violaceum, P. chlororaphis and S. marcescens was enhanced during indole supplementation. Overall, these studies suggest that indole represents a general inhibitor of AHL-based quorum signalling in Gram-negative bacteria.

Indole Biodegradation in Acinetobacter sp. Strain O153: Genetic and Biochemical Characterization

“…This effect was later attributed to the indole-caused inhibition of AHL-based quorum-sensing signaling by altering the folding of the AqsR regulator (14,54). Such an effect was reported for a number of Gram-negative bacteria, including Chromobacterium violaceum, Pseudomonas chlororaphis, Serratia marcescens (55), and Acinetobacter oleivorans DR1 (14), a strain which was identified here to possess the iif-ant operon combination (Fig. 3).…”

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

“…Evidence of host-derived oxidative stress in the middle ear (Table III), concurrent with NTHI-derived tryptophanase, suggests indole production. Indole can inhibit N-acylated homoserine lactone-mediated quorum signaling associated with virulence and biofilm formation in Vibrio species (140). Decreases in indole concentration through changes in bacterial metabolic activity or release of factors that interfere with tryptophanase production, coincides with increased bacterial persistence and increased biofilm formation (142,143).…”

“…Indole is an important intra-and interspecies signaling molecule that regulates bacterial behaviors such as biofilm formation and antibiotic resistance (135,136). In E. coli, indole increases production of multidrug exporter proteins leading to antibiotic resistance, yet decreases biofilm formation through repression of motility and cell adherence (137)(138)(139)(140). Further, endogenous oxidative stress leads to increased tryptophanase, increased indole and delayed biofilm formation (141).…”

Roles of Indole as an Interspecies and Interkingdom Signaling Molecule

“…The inhibition of AHL-mediated quorum signaling by indole is widespread in bacteria, including P. aeruginosa [48,[51][52][53], Acinetobacter oleivorans [54], Chromobacterium violaceum, Pseudomonas chlororaphis, and Serratia marcescens [55] ( Table 1). These results suggest that indole has considerable potential as a QS-quenching agent and as an antivirulence compound against pathogenic bacteria.…”