| Structural highlights
Function
PQSE_PSEAE Required for the biosynthesis of the quorum-sensing signaling molecules 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS), which are important for biofilm formation and virulence. Catalyzes the hydrolysis of the intermediate 2-aminobenzoylacetyl-CoA (2-ABA-CoA) to form 2-aminobenzoylacetate (2-ABA), the precursor of HHQ. In vitro, can also hydrolyze other substrates such as S-ethyl-acetothioacetate and acetoacetyl-CoA, but is inactive against anthraniloyl-CoA, malonyl-CoA and octanoyl-CoA (PubMed:25960261, PubMed:27082157). Beyond its thioesterase function, is involved in the regulation of diverse genes coding for key virulence determinants and biofilm development (PubMed:27851827).[1] [2] [3] RHLR_PSEAE Quorum-sensing regulator that controls the expression of multiple virulence factors in response to extracellular signaling molecules called autoinducers (PubMed:7494482, PubMed:8522523, PubMed:15576196). Involved, among others, in the transcriptional regulation of genes that are responsible for rhamnolipid surfactant biosynthesis (PubMed:8144472, PubMed:7604006, PubMed:14526008). Acts by binding to a specific sequence in the rhlAB regulatory region, both in the presence and in the absence of its autoinducer (PubMed:14526008). In the former case it activates transcription of the promoter, whereas in the latter it acts as a transcriptional repressor (PubMed:14526008). Also regulates the expression of the rmlBDAC operon, encoding dTDP-L-rhamnose biosynthetic enzymes, by binding to the rml box in the promoter region (PubMed:22262098). In addition, is involved in the regulation of the production of elastase (lasB) and pyocyanine (PubMed:8144472, PubMed:7604006, PubMed:8522523).[4] [5] [6] [7] [8] [9] [10]
Publication Abstract from PubMed
Pseudomonas aeruginosa is a major cause of nosocomial infections and also leads to severe exacerbations in cystic fibrosis or chronic obstructive pulmonary disease. Three intertwined quorum sensing systems control virulence of P. aeruginosa, with the rhl circuit playing the leading role in late and chronic infections. The majority of traits controlled by rhl transcription factor RhlR depend on PqsE, a dispensable thioesterase in Pseudomonas Quinolone Signal (PQS) biosynthesis that interferes with RhlR through an enigmatic mechanism likely involving direct interaction of both proteins. Here we show that PqsE and RhlR form a 2:2 protein complex that, together with RhlR agonist N-butanoyl-L-homoserine lactone (C4-HSL), solubilizes RhlR and thereby renders the otherwise insoluble transcription factor active. We determine crystal structures of the complex and identify residues essential for the interaction. To corroborate the chaperone-like activity of PqsE, we design stability-optimized variants of RhlR that bypass the need for C4-HSL and PqsE in activating PqsE/RhlR-controlled processes of P. aeruginosa. Together, our data provide insight into the unique regulatory role of PqsE and lay groundwork for developing new P. aeruginosa-specific pharmaceuticals.
Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa.,Borgert SR, Henke S, Witzgall F, Schmelz S, Zur Lage S, Hotop SK, Stephen S, Lubken D, Kruger J, Gomez NO, van Ham M, Jansch L, Kalesse M, Pich A, Bronstrup M, Haussler S, Blankenfeldt W Nat Commun. 2022 Dec 1;13(1):7402. doi: 10.1038/s41467-022-35030-w. PMID:36456567[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Drees SL, Fetzner S. PqsE of Pseudomonas aeruginosa Acts as Pathway-Specific Thioesterase in the Biosynthesis of Alkylquinolone Signaling Molecules. Chem Biol. 2015 May 21;22(5):611-8. doi: 10.1016/j.chembiol.2015.04.012. Epub , 2015 May 7. PMID:25960261 doi:http://dx.doi.org/10.1016/j.chembiol.2015.04.012
- ↑ Zender M, Witzgall F, Drees SL, Weidel E, Maurer CK, Fetzner S, Blankenfeldt W, Empting M, Hartmann RW. Dissecting the Multiple Roles of PqsE in Pseudomonas aeruginosa Virulence by Discovery of Small Tool Compounds. ACS Chem Biol. 2016 Apr 28. PMID:27082157 doi:http://dx.doi.org/10.1021/acschembio.6b00156
- ↑ Rampioni G, Falcone M, Heeb S, Frangipani E, Fletcher MP, Dubern JF, Visca P, Leoni L, Camara M, Williams P. Unravelling the Genome-Wide Contributions of Specific 2-Alkyl-4-Quinolones and PqsE to Quorum Sensing in Pseudomonas aeruginosa. PLoS Pathog. 2016 Nov 16;12(11):e1006029. doi: 10.1371/journal.ppat.1006029. , eCollection 2016 Nov. PMID:27851827 doi:http://dx.doi.org/10.1371/journal.ppat.1006029
- ↑ Medina G, Juarez K, Valderrama B, Soberon-Chavez G. Mechanism of Pseudomonas aeruginosa RhlR transcriptional regulation of the rhlAB promoter. J Bacteriol. 2003 Oct;185(20):5976-83. doi: 10.1128/JB.185.20.5976-5983.2003. PMID:14526008 doi:http://dx.doi.org/10.1128/JB.185.20.5976-5983.2003
- ↑ Wagner VE, Gillis RJ, Iglewski BH. Transcriptome analysis of quorum-sensing regulation and virulence factor expression in Pseudomonas aeruginosa. Vaccine. 2004 Dec 6;22 Suppl 1:S15-20. doi: 10.1016/j.vaccine.2004.08.011. PMID:15576196 doi:http://dx.doi.org/10.1016/j.vaccine.2004.08.011
- ↑ Aguirre-Ramirez M, Medina G, Gonzalez-Valdez A, Grosso-Becerra V, Soberon-Chavez G. The Pseudomonas aeruginosa rmlBDAC operon, encoding dTDP-L-rhamnose biosynthetic enzymes, is regulated by the quorum-sensing transcriptional regulator RhlR and the alternative sigma factor sigmaS. Microbiology (Reading). 2012 Apr;158(Pt 4):908-916. doi: 10.1099/mic.0.054726-0. , Epub 2012 Jan 19. PMID:22262098 doi:http://dx.doi.org/10.1099/mic.0.054726-0
- ↑ Latifi A, Winson MK, Foglino M, Bycroft BW, Stewart GS, Lazdunski A, Williams P. Multiple homologues of LuxR and LuxI control expression of virulence determinants and secondary metabolites through quorum sensing in Pseudomonas aeruginosa PAO1. Mol Microbiol. 1995 Jul;17(2):333-43. doi: , 10.1111/j.1365-2958.1995.mmi_17020333.x. PMID:7494482 doi:http://dx.doi.org/10.1111/j.1365-2958.1995.mmi_17020333.x
- ↑ Ochsner UA, Reiser J. Autoinducer-mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6424-8. PMID:7604006
- ↑ Ochsner UA, Koch AK, Fiechter A, Reiser J. Isolation and characterization of a regulatory gene affecting rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa. J Bacteriol. 1994 Apr;176(7):2044-54. doi: 10.1128/jb.176.7.2044-2054.1994. PMID:8144472 doi:http://dx.doi.org/10.1128/jb.176.7.2044-2054.1994
- ↑ Brint JM, Ohman DE. Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the autoinducer-responsive LuxR-LuxI family. J Bacteriol. 1995 Dec;177(24):7155-63. PMID:8522523
- ↑ Borgert SR, Henke S, Witzgall F, Schmelz S, Zur Lage S, Hotop SK, Stephen S, Lubken D, Kruger J, Gomez NO, van Ham M, Jansch L, Kalesse M, Pich A, Bronstrup M, Haussler S, Blankenfeldt W. Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa. Nat Commun. 2022 Dec 1;13(1):7402. doi: 10.1038/s41467-022-35030-w. PMID:36456567 doi:http://dx.doi.org/10.1038/s41467-022-35030-w
|
