The MapZ-Mediated Methylation of Chemoreceptors Contributes to Pathogenicity of Pseudomonas aeruginosa

Abstract

The pathogenic bacterium Pseudomonas aeruginosa is notorious for causing acute and chronic infections in humans. The ability to infect host by P. aeruginosa is dependent on a complex cellular signaling network, which includes a large number of chemosensory signaling pathways that rely on the methyl-accepting chemotaxis proteins (MCPs). We previously found that the second messenger c-di-GMP-binding adaptor MapZ modulates the methylation of an amino acid-detecting MCP by directly interacting with a chemotaxis methyltransferase CheR1. The current study further expands our understanding of the role of MapZ in regulating chemosensory pathways by demonstrating that MapZ suppresses the methylation of multiple MCPs in P. aeruginosa PAO1. The MCPs under the control of MapZ include five MCPs (Aer, CtpH, CptM, PctA, and PctB) for detecting oxygen/energy, inorganic phosphate, malate and amino acids, and three MCPs (PA1251, PA1608, and PA2867) for detecting unknown chemoattractant or chemorepellent. Chemotaxis assays showed that overexpression of MapZ hampered the taxis of P. aeruginosa toward chemoattractants and scratch-wounded human cells. Mouse infection experiments demonstrated that a dysfunction in MapZ regulation had a profound negative impact on the dissemination of P. aeruginosa and resulted in attenuated bacterial virulence. Together, the results imply that by controlling the methylation of various MCPs via the adaptor protein MapZ, c-di-GMP exerts a profound influence on chemotactic responses and bacterial pathogenesis.

Taming the flagellar motor of pseudomonads with a nucleotide messenger

“…The involvement of the MapZmediated pathway in biofilm formation is consistent with the roles played by DipA, NbdA and RbdA in biofilm formation (An et al, 2010b;Roy et al, 2012;Li et al, 2013;2014;Liu et al, 2018). Mouse infection experiments demonstrated that a defective MapZ or imbalanced expression of MapZ can negatively impact the dissemination of P. aeruginosa in the host and cause attenuated bacterial virulence (Sheng et al, 2019). Hence, it seems that the control of flagellar motor switching, along with motor torque/speed control, must be taken into consideration when interpreting the behaviour and pathogenicity of pseudomonads.…”

“…Unlike the Che system, the Che2 system may only have a specialized function in the stationary phase of growth (Guvener et al, 2006). As a component of the Che system, the methyltransferase CheR1 (PA3348) methylates at least eight MCPs, including the ones that sense amino acids, phosphate and energy status (Sheng et al, 2019). Recent studies established that c-di-GMP controls the switching of the flagellar motor of P. aeruginosa by interfering with the chemosensory signalling systems.…”

Regulation of flagellar motor switching by c-di-GMP phosphodiesterases in Pseudomonas aeruginosa

“…Our recent studies revealed that the c-di-GMP-binding adaptor protein MapZ plays a crucial role in regulating flagellar motor switching in P. aeruginosa (19 -21). At high c-di-GMP concentrations, MapZ binds to the methyltransferase CheR1 and inhibits its enzymatic activity to decrease the methylation of multiple methyl-accepting chemotaxis proteins (MCPs) (22). The MapZ-mediated mechanism is likely to be operational in other Pseudomonas species considering mapZ is one of the most conserved nonessential genes in the genus of Pseudomonas (23).…”

Advances in Bacterial Biofilm Management for Maintaining Microbiome Homeostasis

“…This initial reversible attachment of microbes onto the targeted surfaces relies on the master regulator CsgD to activate the production of cellulose, curli, and fimbriae that plays a vital role in surface adherence (Figure 1B). [ 9 ] Further, the CsgD will activate the csgBAC needed for the upregulation of cyclic di‐guanylate (c‐di‐GMP). c‐di‐GMP represses the flagellar operons that switch the counterclockwise rotation of the bundled flagella to clockwise rotation, slowing down the microbe for surface adherence.…”

“…Through the interaction of c‐di‐GMP with PilZ proteins such as MapZ from Pseudomonas aeruginosa , the flagellar movement reverts to low switching frequency providing the opportunity for the flagella and newly formed curli and fimbriae to attach on the target surface. [ 9,10 ] The microbial adhesion on tissue‐ and abiotic‐ surfaces result from the nature of flagellin protein and adhesive properties of CsgA subunit of curli fibers that interact through polar, non‐polar and protein‐specific interactions. [ 11,12 ] In the irreversible attachment, the repression of Carbon Storage Regulatory system A (CsrA/RsmA) through sensing the changes in the environmental cues, relieves the repression of psl, glgCAP , and pgaABCD .…”