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.
Highlights
The opportunistic pathogen Pseudomonas aeruginosa is capable of causing severe and potentially lethal infections in immunocompromised patients
It was shown previously that the chemotaxis methyltransferase CheR1 of P. aeruginosa methylates PctA, one of the methyl-accepting chemotaxis proteins (MCPs) involved in sensing amino acids (Schmidt et al, 2011)
There are 22 more membrane-bound MCPs in P. aeruginosa PAO1 and it was not known how many of the MCPs are methylated by CheR1
Summary
The opportunistic pathogen Pseudomonas aeruginosa is capable of causing severe and potentially lethal infections in immunocompromised patients. Among the MCPs, PA2561(CtpH)/PA4844 (CtpL) (Wu et al, 2000; Rico-Jimenez et al, 2016), PA2652(CtpM) (Alvarez-Ortega and Harwood, 2007; Martin-Mora et al, 2018), PA4309 (PctA)/PA4310 (PctB)/PA4307 (PctC) (Taguchi et al, 1997; Rico-Jimenez et al, 2013), PA1561 (Aer, formerly known as TlpC) (Hong et al, 2004), PA0176 (Aer2) (Hong et al, 2004), PA2654(TlpQ) (Kim et al, 2007), PA0180(CttP) (Kim et al, 2006), and PA5072(McpK) (Martin-Mora et al, 2016) have been shown to be responsible for detecting ligands such as inorganic phosphate, malate, amino acids and gamma aminobutyrate (GABA), oxygen, ethylene, chloroethylenes, and α-ketoglutarate It is not known how many of the 23 MCPs are methylated by CheR1, and subjected to the control of MapZ and c-di-GMP.
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