Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR in Pseudomonas aeruginosa. Issue 5 (18th August 2020)

• Record Type: Journal Article
• Authors: Wang, Tietao; Qi, Yihang; Wang, Zhihan; Zhao, Jingru; Ji, Linxuan; Li, Jun; Cai, Zhao; Yang, Liang; Wu, Min; Liang, Haihua
• Is Part Of: Molecular microbiology. Volume 114:Issue 5(2020)
• Page Start: 857
• Page End: 869
• Publication Date: 2020-08-18
• Subjects: anthranilate metabolism -- bacterial virulence -- GntR family regulator -- Pseudomonas aeruginosa -- quorum‐sensing system; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14584
• Languages: English
• ISSNs: 0950-382X

Abstract

Abstract: The GntR family regulators are widely distributed in bacteria and play critical roles in metabolic processes and bacterial pathogenicity. In this study, we describe a GntR family protein encoded by PA4132 that we named MpaR (M vfR‐mediated P QS and a nthranilate r egulator) for its regulation of Pseudomonas quinolone signal (PQS) production and anthranilate metabolism in Pseudomonas aeruginosa . The deletion of mpaR increased biofilm formation and reduced pyocyanin production. RNA sequencing analysis revealed that the mRNA levels of antABC encoding enzymes for the synthesis of catechol from anthranilate, a precursor of the PQS, were most affected by mpaR deletion. Data showed that MpaR directly activates the expression of mvfR, a master regulator of pqs system, and subsequently promotes PQS production. Accordingly, deletion of mpaR activates the expression of antABC genes, and thus, increases catechol production. We also demonstrated that MpaR represses the rhl quorum‐sensing (QS) system, which has been shown to control antABC activity. These results suggested that MpaR function is integrated into the QS regulatory network. Moreover, mutation of mpaR promotes bacterial survival in a mouse model of acute pneumonia infection. Collectively, this study identified a novel regulator of pqs system, which coordinately controls anthranilate metabolism and bacterial virulence in P . aeruginosa . Abstract : We identify a GntR family regulator, MpaR, which regulates anthranilate metabolism and pyocyanin production by activation of pqs system directly or repression of rhl system. Additionally, MpaR is involved in regulation of biofilm formation and bacterial pathogenicity. These findings highlight how intermediary metabolism is interconnected with bacterial pathogenesis in P. aeruginosa .