Indole: a signaling molecule or a mere metabolic byproduct that alters bacterial physiology at a high concentration?

Abstract

Indole is an organic compound that is widespread in microbial communities inhabiting diverse habitats, like the soil environment and human intestines. Measurement of indole production is a traditional method for the identification of microbial species. Escherichia coli can produce millimolar concentrations of indole in the stationary growth phase under nutrient-rich conditions. Indole has received considerable attention because of its remarkable effects on various biological functions of the microbial communities, for example, biofilm formation, motility, virulence, plasmid stability, and antibiotic resistance. Indole may function as an intercellular signaling molecule, like a quorum-sensing signal. Nevertheless, a receptor system for indole and the function of this compound in coordinated behavior of a microbial population (which are requirements for a true signaling molecule) have not yet been confirmed. Recent findings suggest that a long-known quorum-sensing regulator, E. coli's SdiA, cannot recognize indole and that this compound may simply cause membrane disruption and energy reduction, which can lead to various changes in bacterial physiology including unstable folding of a quorum-sensing regulator. Indole appears to be responsible for acquisition of antibiotic resistance via the formation of persister cells and activation of an exporter. This review highlights and summarizes the current knowledge about indole as a multitrophic molecule among bacteria, together with recently identified new avenues of research.

Indole-Induced Activities of β-Lactamase and Efflux Pump Confer Ampicillin Resistance in Pseudomonas putida KT2440

“…Indole has received considerable attention because of its broad range of effects on various microbial functions (Kim and Park, 2015). Indole increases AMR through the expression of transporter and stress resistance genes and the formation of bacterial persister cells (Hirakawa et al, 2005; Vega et al, 2012, 2013; Molina-Santiago et al, 2014).…”

“…The fact that indole affected cell physiologies at a low concentration should not be overlooked, because indole is widespread in natural environments and is volatile. Millmolar concentrations of indole can be toxic and inhibit growth (Kim et al, 2013; Kim and Park, 2015; Lee et al, 2015a), protein folding (Kim and Park, 2013) and cell division, acting as a proton ionophore (Chimerel et al, 2012). Indole can increase the NADH/NAD + ratio and decrease the ATP concentration in cells because of perturbations in the membrane potential when indole is transported across the cell membrane (Piñero-Fernandez et al, 2011; Chimerel et al, 2012; Kim et al, 2013).…”

Gut bacteria-derived molecules as mediators and markers in cardiovascular diseases. The role of the gut-blood barrier

“…Research suggests that indole may be involved in intracellular signalling, biofilm formation, and antibiotic resistance in bacteria [30]. However, its role in the circulatory system has not yet been elucidated.…”

“…Heart failure development [48] Indoles Intracellular signalling, biofilm formation, antibiotic resistance in bacteria [30] Accumulation in patients with CKD [9] Impairment of antioxidation and promotion of free radical formation [9] Promotion of endothelium dysfunction: decreased production of nitric oxide, increased production of reactive oxygen species [9] Hypertrophy of cardiac myocytes and production of collagen by cardiac fibroblasts [32] Decrease of indole concentration is beneficial in CKD [31] Correlation of high concentration of indoxyl sulphate with aortic lesion formation and mortality in CKD [9] Pro-arrhythmogenic potential [9] Association with CV events and mortality in CKD [49] Short-chain fatty acids Energy source of colonic cells and pH regulating agents…”

Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

“…The age-old paradigm that bacterial metabolites, specifically, indoles as being generally toxic compounds, are not supported by the evidence as they are naturally present in micro-to millimolar amounts in humans [52]. Bacterial targets for indole remain elusive [53]. Bacteria specific indole metabolites include indole-3-propionic acid (IPA), among others.…”