Chemotaxis of the Human Pathogen Pseudomonas aeruginosa to the Neurotransmitter Acetylcholine

Abstract

P. aeruginosa causes a significant number of deaths annually worldwide. For many pathogens, chemotaxis plays an import role in the initial stages of infection, and deciphering the key chomoeffectors and their cognate chemoreceptors may permit the development of strategies to inhibit this process.

The pH Robustness of Bacterial Sensing

“…There is an almost unlimited number of different ligands that bind to extracytosolic LBDs, which can thus be used for the development of novel biosensors. These compounds include clinically important compounds such as the neurotransmitters epinephrine ( 77 ), γ-aminobutyric acid (GABA) ( 56 ), histamine ( 78 ) or acetylcholine ( 79 ), antimicrobial peptides ( 80 ), amino acids ( 40 ), organic acids ( 46 ), sugars ( 81 ), fatty acids ( 82 ), quorum-sensing molecules ( 39 ), plant hormones ( 83 ), aromatic hydrocarbons ( 84 ), purines ( 41 ), polyamines ( 25 ), quaternary amines ( 85 ), nitrate ( 86 ), inorganic phosphate ( 87 ), and specific metal cations ( 88 ) or oxanions ( 30 ). The demonstration that extracytosolic LBDs maintain their capacity to sense their ligands over a wide pH range will permit the construction of biosensors that are robust and able to withstand changes in the analyte medium.…”

“…Chemotaxis assays were performed as previously described ( 79 ) with some modifications. When cultures reached an OD 660 of 0.4, the cells were gently washed twice with chemotaxis buffer at different pH and then resuspended in fresh buffer.…”

The Cellular Abundance of Chemoreceptors, Chemosensory Signaling Proteins, Sensor Histidine Kinases, and Solute Binding Proteins of Pseudomonas aeruginosa Provides Insight into Sensory Preferences and Signaling Mechanisms

“…To this end, we selected chemoreceptors that showed significant variation in different growth media and for which it was shown that the mutation of the corresponding gene abolished chemotaxis to a given chemoattractant. These receptors were PctC, PctD, and McpK, for which we have shown previously that a deletion or inactivation of the corresponding gene has suppressed chemotaxis to GABA [ 72 ], choline [ 20 ], or α-ketoglutarate [ 77 ], respectively. This implies that responses of the wild type strain to these compounds are entirely due to the action of these receptors.…”

“…Whereas in a canonical two-component system one sensor protein controls the phosphorylation state of its cognate response regulator, in chemosensory pathways typically many chemoreceptors control the phosphorylation state of CheY. Chemoreceptor abundance is thus proposed to define the weight by which a given receptor contributes to defining the final response, as supported by different studies in which specific chemoreceptors were overexpressed [ 20 , 21 , 22 , 23 ]. Here we have used proteomics to analyze chemoreceptor protein amounts in P. aeruginosa —a model bacterium in the field of signal transduction [ 9 , 32 ].…”

“…The abundance of the 10 chemoreceptors in Bacillus subtilis has been quantified by immunoblot and differed by a factor of about 40 [ 17 ]. A number of studies demonstrate that chemoeffector affinity for its chemoreceptor determines the onset of response [ 18 , 19 , 20 ], whereas the cellular amount of chemoreceptors appears to be related to the magnitude of chemotaxis, since chemoreceptor overexpression increases chemotaxis [ 20 , 21 , 22 , 23 ].…”