Deciphering the Che2 chemosensory pathway and the roles of individual Che2 proteins from Pseudomonas aeruginosa

Abstract

Bacterial chemosensory systems sense and respond to stimuli via chemoreceptors that activate phosphotransfer cascades and initiate cellular responses. Pseudomonas aeruginosa has four chemosensory systems, three of which regulate biofilm formation (the Wsp system), twitching motility (the Pil-Chp system), and flagellum-mediated chemotaxis (the Che system) (Kato et al., 2008; Sampedro et al., 2014). The role of P. aeruginosa's fourth chemosensory system, Che2, is not well understood, although it appears to be involved in stress responses and it impacts virulence (Garvis et al., 2009; Schuster et al., 2004). The P. aeruginosa chemotaxis system receives sensory input from 23 chemoreceptors, whereas the three additional chemosensory systems employ one receptor each (Ortega et al., 2017). The receptor for Che2 is Aer2 (McpB) and it is encoded within the che2 operon [(Hong et al., 2004), Figure 1a]. Che2 proteins (Y2, A2, W2, Aer2, R2, D, and B2) are expressed in stationary phase and form an Aer2-mediated complex near the cell pole that does not co-localize with chemotaxis proteins [(Guvener et al., 2006; Schuster et al., 2004; Yang and Briegel, 2020), Figure 1b]. The stimulus for Che2 is O 2 , which binds to the PAS-heme domain of Aer2 with the assistance of a Trp residue that rotates to bond with O 2 [(Airola et al., 2013;

Evidence for Pentapeptide-Dependent and Independent CheB Methylesterases

“…The data thus show that, exclusively, the CheR and CheB homologs encoded by the Che 2 gene cluster ( Figure 1 ) bind to McpB, the only receptor predicted to stimulate the Che 2 pathway [ 33 ]. This pathway is essential for the full virulence of P. aeruginosa [ 39 , 56 ], but its precise function still needs to be determined [ 37 ]. McpB and Che 2 pathway homologs are widespread in pathogenic and nonpathogenic γ-Proteobacteria [ 57 ], suggesting a function that is not exclusively associated with virulence.…”

“…As shown in Figure 1 , each chemosensory pathway contains a CheR and CheB homolog. Experimental and bioinformatic studies indicate that, of the 26 chemoreceptors, McpB (synonym Aer2) ( Figure 1 ) is the sole chemoreceptor that feeds into the Che 2 pathway [ 33 , 37 ]. Furthermore, it is the only chemoreceptor with a C-terminal pentapeptide [ 13 ].…”

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

“…Whereas the Che pathway mediates chemotaxis, the Wsp (wrinkly spreader phenotype) pathway controls c-di-GMP levels, and the Chp (chemosensory pili) pathway is associated with type IV pili-based motility [ 9 ]. The function of the Che2 pathway is currently less clear, but it was found to tune the behavior of the Che pathway according to the levels of O 2 sensed by McpB/Aer2 [ 33 ] and is required for full virulence [ 9 , 34 , 35 ]. P. aeruginosa PAO1, the model strain of this work, has 26 chemoreceptors ( Figure 2 ), a number well above the bacterial average of 14 [ 36 ].…”

Oxygen-Induced Conformational Changes in the PAS-Heme Domain of the Pseudomonas aeruginosa Aer2 Receptor

“…The kinase control module of Aer2 regulates the autophosphorylation of a bound histidine kinase, CheA2, to initiate a cascade of signaling events. 11 The linear arrangement of Aer2 dimers results in minimal PAS-HAMP interactions, in contrast to the aerotaxis receptor, Aer, in which PAS signals are relayed through side-on PAS-HAMP domain interactions. 8,12,13 In Aer2, signals are theoretically conveyed from the PAS-sensing domain via the last PAS element, Iβ, directly to downstream HAMP domains 4 and 5 (Figure 1).…”

“…The Aer2 receptor from Pseudomonas aeruginosa is an O 2 sensor that has an unusual linear domain arrangement with its PAS-sensing domain sandwiched between three N-terminal and two C-terminal HAMP domains, followed by a kinase control module that is common to all MCPs (Figure A). The kinase control module of Aer2 regulates the autophosphorylation of a bound histidine kinase, CheA2, to initiate a cascade of signaling events . The linear arrangement of Aer2 dimers results in minimal PAS-HAMP interactions, in contrast to the aerotaxis receptor, Aer, in which PAS signals are relayed through side-on PAS-HAMP domain interactions. ,, In Aer2, signals are theoretically conveyed from the PAS-sensing domain via the last PAS element, Iβ, directly to downstream HAMP domains 4 and 5 (Figure ).…”