Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR inPseudomonas aeruginosa

Wang, Tietao1; Qi, Yihang1; Wang, Zhihan2; Zhao, Jingru1; Ji, Linxuan1; Li, Jun3; Cai, Zhao4; Yang, Liang4; Wu, Min5; Liang, Haihua1

2020-08-18

10.1111/mmi.14584

MOLECULAR MICROBIOLOGY   影响因子和分区

0950-382X

1365-2958

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 (MvfR-mediatedPQS andanthranilateregulator) for its regulation ofPseudomonasquinolone signal (PQS) production and anthranilate metabolism inPseudomonas aeruginosa. The deletion ofmpaRincreased biofilm formation and reduced pyocyanin production. RNA sequencing analysis revealed that the mRNA levels ofantABCencoding enzymes for the synthesis of catechol from anthranilate, a precursor of the PQS, were most affected bympaRdeletion. Data showed that MpaR directly activates the expression ofmvfR, a master regulator ofpqssystem, and subsequently promotes PQS production. Accordingly, deletion ofmpaRactivates the expression ofantABCgenes, and thus, increases catechol production. We also demonstrated that MpaR represses therhlquorum-sensing (QS) system, which has been shown to controlantABCactivity. These results suggested that MpaR function is integrated into the QS regulatory network. Moreover, mutation ofmpaRpromotes bacterial survival in a mouse model of acute pneumonia infection. Collectively, this study identified a novel regulator ofpqssystem, which coordinately controls anthranilate metabolism and bacterial virulence inP.aeruginosa.

anthranilate metabolism bacterial virulence GntR family regulator Pseudomonas aeruginosa quorum-sensing system

SCI

英语

其他

National Natural Science Foundation of China[31622003][31670080][31870060][31800127] ; Shaanxi science and technology innovation team[2019TD-016] ; Guangdong Natural Science Funds for Distinguished Yong Scholar[2020B151502089] ; China Postdoctoral Science Foundation[2018M641008] ; Postdoctoral Science Research Plan in ShaanXi Province of China[2018BSHEDZZ244]

Biochemistry & Molecular Biology ; Microbiology

Biochemistry & Molecular Biology ; Microbiology

WOS:000560250000001

WILEY

MICROBIOLOGY

Web of Science

1.Northwest Univ, Coll Life Sci, Key Lab Resources Biol & Biotechnol Western China, Minist Educ, Xian 710069, Shaanxi, Peoples R China
2.Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu, Peoples R China
3.Zhejiang Univ Technol, Coll Bioengn & Biotechnol, Hangzhou, Peoples R China
4.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China
5.Univ North Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND USA

Wang, Tietao,Qi, Yihang,Wang, Zhihan,et al. Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR inPseudomonas aeruginosa[J]. MOLECULAR MICROBIOLOGY,2020.

Wang, Tietao.,Qi, Yihang.,Wang, Zhihan.,Zhao, Jingru.,Ji, Linxuan.,...&Liang, Haihua.(2020).Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR inPseudomonas aeruginosa.MOLECULAR MICROBIOLOGY.

Wang, Tietao,et al."Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR inPseudomonas aeruginosa".MOLECULAR MICROBIOLOGY (2020).