Local and Universal Action: The Paradoxes of Indole Signalling in Bacteria

The role of indole in a wide range of stress responses is explored and explanations for the lack of consistency in the scientific literature are discussed. In view of the absence of a defined indole receptor protein, we discuss a proposal that the cell membrane is the primary target. The accumulation of indole in cell membranes, as well as its ability to pass thorough membranes in the absence of a protein transporter, offer explanations for its promiscuous effects on bacteria and eukaryotic cells. Indole signalling is exerted through one of two modes: a long-lasting but low-level (persistent) signal or a transient, high-level (pulse) signal. Persistent signalling mediates resistance to multiple stresses, including persister and biofilm formation, while pulse signalling has been shown to contribute to E. coli survival under starvation and the regulation of cytoplasmic pH. Indole is a signalling molecule produced by many bacterial species and involved in intraspecies, interspecies, and interkingdom signalling. Despite the increasing volume of research published in this area, many aspects of indole signalling remain enigmatic. There is disagreement over the mechanism of indole import and export and no clearly defined target through which its effects are exerted. Progress is hindered further by the confused and sometimes contradictory body of indole research literature. We explore the reasons behind this lack of consistency and speculate whether the discovery of a new, pulse mode of indole signalling, together with a move away from the idea of a conventional protein target, might help to overcome these problems and enable the field to move forward. Indole is a signalling molecule produced by many bacterial species and involved in intraspecies, interspecies, and interkingdom signalling. Despite the increasing volume of research published in this area, many aspects of indole signalling remain enigmatic. There is disagreement over the mechanism of indole import and export and no clearly defined target through which its effects are exerted. Progress is hindered further by the confused and sometimes contradictory body of indole research literature. We explore the reasons behind this lack of consistency and speculate whether the discovery of a new, pulse mode of indole signalling, together with a move away from the idea of a conventional protein target, might help to overcome these problems and enable the field to move forward.