Indole is synthesized from the amino acid tryptophan through a series of enzymatic reactions primarily facilitated by the enzyme tryptophanase (TnaA). Initially, tryptophan, either obtained from the environment or synthesized de novo, is taken up by bacterial cells. Tryptophanase catalyzes the conversion of tryptophan into indole, along with ammonia and pyruvate. During this process, indole-3-pyruvate may also form as an intermediate; however, the dominant pathway culminates directly in the production of indole. Once synthesized, indole plays a significant role in quorum sensing, functioning as a signaling molecule that allows bacteria to communicate and coordinate their behavior based on cell density. Indole's influence extends to various physiological processes; it can modulate gene expression without requiring specific receptor binding, thus affecting behaviors such as biofilm formation and virulence. For instance, it has been shown to enhance the expression of drug resistance genes in non-indole-producing Salmonella enterica strains. Additionally, indole's ability to interact with host cells leads to modulation of immune responses and maintenance of epithelial barrier functions. By activating receptors such as the pregnane X receptor (PXR) and aryl hydrocarbon receptor (AHR), indole mediates important interspecies signaling in the gut microbiome, ultimately influencing the dynamics of bacterial communities and their interactions with the host. Through these diverse mechanisms, indole emerges as a critical signaling metabolite, enabling bacteria to adapt and thrive in complex environments.

Quorum Sensing: Indole Biosynthesis and Biofilm Formation References