Trends in Microbiology
Volume 23, Issue 11, November 2015, Pages 707-718
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Review
Roles of Indole as an Interspecies and Interkingdom Signaling Molecule

https://doi.org/10.1016/j.tim.2015.08.001Get rights and content

Trends

A variety of bacteria, and some plants, produce large quantities of indole, and thus, indole and its derivatives are widespread in prokaryotic and eukaryotic communities. Recently, indole was shown to be an intercellular, interspecies, and interkingdom signaling molecule.

Indole and its derivatives can suppress the bacterial pathogenesis of several antibiotic-resistant pathogens by inhibiting quorum sensing and virulence factor production.

Insects sense indole, which controls their behavior. Furthermore, indole controls plant defense systems and growth, and modulates oxidative stress, intestinal inflammation, and hormone secretion in animals. Emerging data suggest that indoles may influence human diseases, such as inflammatory, neurological, and metabolic diseases.

A number of bacteria, and some plants, produce large quantities of indole, which is widespread in animal intestinal tracts and in the rhizosphere. Indole, as an interspecies and interkingdom signaling molecule, plays important roles in bacterial pathogenesis and eukaryotic immunity. Furthermore, indole and its derivatives are viewed as potential antivirulence compounds against antibiotic-resistant pathogens because of their ability to inhibit quorum sensing and virulence factor production. Indole modulates oxidative stress, intestinal inflammation, and hormone secretion in animals, and it controls plant defense systems and growth. Insects and nematodes can recognize indole, which controls some of their behavior. This review presents current knowledge regarding indole and its derivatives, their biotechnological applications and their role in prokaryotic and eukaryotic systems.

Section snippets

Intercellular, Interspecies, and Interkingdom Signaling by Indole and Its Derivatives

Bacteria and eukaryotes coexist in the natural environment, and bacterial metabolites modulate eukaryotic immunity. The commensal bacteria colonize the surfaces of animal and plant cells and prevent invasion by pathogenic bacteria [1]. In fact, an imbalance between commensal (or symbiotic) and pathogenic bacteria can result in life-threatening infections. Bacteria produce a wide variety of signaling molecules, siderophores, and antibiotics. Other organisms can sense these signaling molecules,

Functions and Applications of Indole and Its Derivatives in Indole-Producing Bacteria

Indole biosynthesis and its regulation were well studied during the last century, and its biological functions have been extensively investigated during the last decade, mostly in indole-producing bacteria 3, 27. Indole is considered by some authors to be an intercellular signaling molecule, like a quorum-sensing (QS) signal 11, 12, 31, and it controls diverse aspects of bacterial physiology [27].

Recently, indole was shown to modulate antibiotic resistance and persister formation in E. coli.

Antivirulence Activities of Indoles against Non-Indole-Producing Microorganisms

In the natural environment, most bacteria survive in multispecies communities, and thus, compete for resources and space, but they are also able to interfere with, or utilize, signaling molecules from other bacteria. Indole is an interspecies signaling molecule; in fact, it was initially reported that indole stimulates biofilm formation by Pseudomonas aeruginosa [3], which is probably due to the degradation of anthranilate [47]. Indole also downregulates P. aeruginosa virulence and QS-regulated

The Impact of Indole on Human Diseases

The human intestinal tract is rich in a diverse range of about 1014 commensal bacteria, some of which are crucial for nutrient assimilation and benefit the immune system [70]. Indole has been detected in the mouse and human gut at concentrations ∼250–1100 μM, but animal cells cannot synthesize indole 5, 6. Furthermore, gut-bacteria-derived indoles, such as indoxyl sulfate, indole-3-propionic acid, isatin, and 5-hydroxyindole (Figure 2), are present in blood, peripheral tissues, urine, and even

Roles of Indole in Plants, Insects, and the Soil Environment

Various plants release volatile compounds in response to herbivore insect attack, and some plants, including maize, are able to synthesize indole using indole-3-glycerol phosphate lyases (Figure 1) [16]. In addition, animal feces are indole-rich and indole-producing rhizobacteria are widespread in soils (Figure 3). Herbivore attack activates the expression of indole-3-glycerol phosphate lyases to enable indole emission by maize [17]. The release of indole is herbivore-specific in maize and is

Concluding Remarks

Soils and the gastrointestinal tracts of animals contain high levels of indole, and it is now evident that indole and its derivatives are considerably more important as interkingdom signals than was originally believed. As an intercellular and interspecies bacterial signaling molecule, indole plays many roles in bacterial pathogenesis. Recently, studies were commenced on the effects of indole on worms, insects, plants, and animals. Furthermore, indole and its derivatives originating from

Acknowledgments

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (#2015R1A2A2A01004542 to J. Lee) and Basic Science Research Program through the NRF funded by the Ministry of Education (#215C000232 to J-H. Lee). T. K. Wood is supported by the Army Research Office (W911NF-14-1-0279).

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