The SiaA/B/C/D Signaling Network Regulates Biofilm Formation in Pseudomonas Aeruginosa

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2020 Feb 25

PMID 32090355

Citations 19

Authors

Gukui Chen

Jianhua Gan

Chun Yang

Yili Zuo

Juan Peng

Meng Li

Weiping Huo

Yingpeng Xie

Yani Zhang

Tietao Wang

Xin Deng

Haihua Liang

Affiliations

Soon will be listed here.

Abstract

Bacterial cyclic-di-GMP (c-di-GMP) production is associated with biofilm development and the switch from acute to chronic infections. In Pseudomonas aeruginosa, the diguanylate cyclase (DGC) SiaD and phosphatase SiaA, which are co-transcribed as part of a siaABCD operon, are essential for cellular aggregation. However, the detailed functions of this operon and the relationships among its constituent genes are unknown. Here, we demonstrate that the siaABCD operon encodes for a signaling network that regulates SiaD enzymatic activity to control biofilm and aggregates formation. Through protein-protein interaction, SiaC promotes SiaD diguanylate cyclase activity. Biochemical and structural data revealed that SiaB is an unusual protein kinase that phosphorylates SiaC, whereas SiaA phosphatase can dephosphorylate SiaC. The phosphorylation state of SiaC is critical for its interaction with SiaD, which will switch on or off the DGC activity of SiaD and regulate c-di-GMP levels and subsequent virulence phenotypes. Collectively, our data provide insights into the molecular mechanisms underlying the modulation of DGC activity associated with chronic infections, which may facilitate the development of antimicrobial drugs.

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References

Becher A, Schweizer H . Integration-proficient Pseudomonas aeruginosa vectors for isolation of single-copy chromosomal lacZ and lux gene fusions. Biotechniques. 2000; 29(5):948-50, 952. DOI: 10.2144/00295bm04. View

Hunter T . Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 1995; 80(2):225-36. DOI: 10.1016/0092-8674(95)90405-0. View

Baraquet C, Murakami K, Parsek M, Harwood C . The FleQ protein from Pseudomonas aeruginosa functions as both a repressor and an activator to control gene expression from the pel operon promoter in response to c-di-GMP. Nucleic Acids Res. 2012; 40(15):7207-18. PMC: 3424551. DOI: 10.1093/nar/gks384. View

Simm R, Morr M, Kader A, Nimtz M, Romling U . GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility. Mol Microbiol. 2004; 53(4):1123-34. DOI: 10.1111/j.1365-2958.2004.04206.x. View

Su B, Ji Y, Sun X, Liu X, Chen Z . Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest and presynaptic docking contribute to BDNF-enhanced synaptic transmission. J Biol Chem. 2013; 289(3):1213-26. PMC: 3894308. DOI: 10.1074/jbc.M113.526129. View

West S, Schweizer H, Dall C, Sample A, Runyen-Janecky L . Construction of improved Escherichia-Pseudomonas shuttle vectors derived from pUC18/19 and sequence of the region required for their replication in Pseudomonas aeruginosa. Gene. 1994; 148(1):81-6. DOI: 10.1016/0378-1119(94)90237-2. View

Schmidt A, Ryjenkov D, Gomelsky M . The ubiquitous protein domain EAL is a cyclic diguanylate-specific phosphodiesterase: enzymatically active and inactive EAL domains. J Bacteriol. 2005; 187(14):4774-81. PMC: 1169503. DOI: 10.1128/JB.187.14.4774-4781.2005. View

Aravind L, Ponting C . The cytoplasmic helical linker domain of receptor histidine kinase and methyl-accepting proteins is common to many prokaryotic signalling proteins. FEMS Microbiol Lett. 1999; 176(1):111-6. DOI: 10.1111/j.1574-6968.1999.tb13650.x. View

Schmidt A, Hammerbacher A, Bastian M, Nieken K, Klockgether J, Merighi M . Oxygen-dependent regulation of c-di-GMP synthesis by SadC controls alginate production in Pseudomonas aeruginosa. Environ Microbiol. 2016; 18(10):3390-3402. DOI: 10.1111/1462-2920.13208. View

10.

Zhu B, Liu C, Liu S, Cong H, Chen Y, Gu L . Membrane association of SadC enhances its diguanylate cyclase activity to control exopolysaccharides synthesis and biofilm formation in Pseudomonas aeruginosa. Environ Microbiol. 2016; 18(10):3440-3452. DOI: 10.1111/1462-2920.13263. View

11.

Terwilliger T, Adams P, Read R, McCoy A, Moriarty N, Grosse-Kunstleve R . Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard. Acta Crystallogr D Biol Crystallogr. 2009; 65(Pt 6):582-601. PMC: 2685735. DOI: 10.1107/S0907444909012098. View

12.

Campbell E, Masuda S, Sun J, Muzzin O, Olson C, Wang S . Crystal structure of the Bacillus stearothermophilus anti-sigma factor SpoIIAB with the sporulation sigma factor sigmaF. Cell. 2002; 108(6):795-807. DOI: 10.1016/s0092-8674(02)00662-1. View

13.

Murshudov G, Skubak P, Lebedev A, Pannu N, Steiner R, Nicholls R . REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):355-67. PMC: 3069751. DOI: 10.1107/S0907444911001314. View

14.

Kelley L, Mezulis S, Yates C, Wass M, Sternberg M . The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015; 10(6):845-58. PMC: 5298202. DOI: 10.1038/nprot.2015.053. View

15.

Brencic A, Lory S . Determination of the regulon and identification of novel mRNA targets of Pseudomonas aeruginosa RsmA. Mol Microbiol. 2009; 72(3):612-32. PMC: 5567987. DOI: 10.1111/j.1365-2958.2009.06670.x. View

16.

Giacovazzo C, Siliqi D . Phasing via SAD/MAD data: the method of the joint probability distribution functions. Acta Crystallogr D Biol Crystallogr. 2003; 60(Pt 1):73-82. DOI: 10.1107/s0907444903022406. View

17.

Irie Y, Borlee B, OConnor J, Hill P, Harwood C, Wozniak D . Self-produced exopolysaccharide is a signal that stimulates biofilm formation in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2012; 109(50):20632-6. PMC: 3528562. DOI: 10.1073/pnas.1217993109. View

18.

Hickman J, Tifrea D, Harwood C . A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. Proc Natl Acad Sci U S A. 2005; 102(40):14422-7. PMC: 1234902. DOI: 10.1073/pnas.0507170102. View

19.

Ross P, Weinhouse H, Aloni Y, Michaeli D, Weinberger-Ohana P, Mayer R . Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid. Nature. 1987; 325(6101):279-81. DOI: 10.1038/325279a0. View

20.

Orr M, Donaldson G, Severin G, Wang J, Sintim H, Waters C . Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover. Proc Natl Acad Sci U S A. 2015; 112(36):E5048-57. PMC: 4568665. DOI: 10.1073/pnas.1507245112. View