Pseudomonas aeruginosa Performs Chemotaxis to All Major Human Neurotransmitters

Abstract

The ubiquitous pathogen Pseudomonas aeruginosa is attracted to γ-aminobutyrate (GABA), acetylcholine, histamine, serotonin, epinephrine, norepinephrine, dopamine, tyramine, glycine, and glutamate via chemotaxis. These compounds are all major neurotransmitters in humans. They are also found in various non-neuronal tissues and are synthesised by different organisms, including bacteria, protozoa, invertebrates, and plants. Many of these neurotransmitters increase the expression of virulence-related genes in P. aeruginosa, so that chemotaxis to these compounds may constitute an important virulence factor. The chemotactic response is initiated by the direct binding of these compounds to the dCache ligand-binding domains of the PctC, TlpQ, PctD, PctA, and PctB chemoreceptors. Previous studies have shown that Escherichia coli is attracted to epinephrine, norepinephrine, and dopamine. These responses are mediated by the Tar and Tsr chemoreceptors, which possess four-helix bundle-type ligand-binding domains. The use of structurally dissimilar chemoreceptors to mediate neurotransmitter chemotaxis suggests convergent evolution. This article is intended to stimulate the study of the connection between neurotransmitter chemotaxis and virulence in P. aeruginosa and to expand the search for neurotransmitter chemotaxis in other motile bacteria.

Keywords: Pseudomonas aeruginosa; chemoreceptor; chemotaxis; neurotransmitter; signal molecule; signal transduction.

FIGURE 1

Structure of major human neurotransmitters. P. aeruginosa was shown to perform chemotaxis to these compounds.

FIGURE 2

Summary of knowledge of neurotransmitter chemotaxis in E. coli and P. aeruginosa . Schematic view of chemoreceptors, four‐helix bundle (4HB) and dCache type LBDs are shown in yellow and green, respectively; transmembrane regions in red and the HAMP/signalling domains in blue. The black arrows indicate direct binding to the chemoreceptor LBD. Grey arrows indicate that a given chemoreceptor was involved in mediating chemotaxis, but no information on the sensing mechanism is available. 4HB: Four‐helix bundle, DHMA: 3,4‐dihydroxymandelic acid.

FIGURE 3

The three‐dimensional structures of the ligand binding domains of the PctC, TlpQ and PctD chemoreceptors from Pseudomonas aeruginosa in complex with bound neurotransmitters. The panel on the right corresponds to a structural superimposition of the three structures. The ligands are shown in the same colour as the corresponding protein chains. Structures correspond to PDB IDs: 7PRR (TlpQ‐LBD bound to histamine), 6FU4 (PctD‐LBD bound to acetylcholine), and 5LTV (PctC‐LBD bound to GABA).