Dataset Information

Moonlighting chaperone 1 activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa

ABSTRACT: 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 determined crystal structures of the complex and identified residues essential for the interaction. To corroborate the chaperone like activity of PqsE, we designed 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.

INSTRUMENT(S): timsTOF Pro, LTQ Orbitrap Velos

ORGANISM(S): Pseudomonas Aeruginosa Pa14

SUBMITTER: Lothar Jaensch

LAB HEAD: Lothar Jänsch, Wulf Blankenfeldt

PROVIDER: PXD038000 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2017_12_12_PqsE_Fe_CE_R1_01.raw	Raw
	2017_12_12_PqsE_Fe_CE_R1_02.raw	Raw
	2017_12_12_PqsE_Fe_CE_R1_03.raw	Raw
	2017_12_12_PqsE_Fe_E_R1_01.raw	Raw
	2017_12_12_PqsE_Fe_E_R1_02.raw	Raw

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Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa.

Borgert Sebastian Roman SR Henke Steffi S Witzgall Florian F Schmelz Stefan S Zur Lage Susanne S Hotop Sven-Kevin SK Stephen Steffi S Lübken Dennis D Krüger Jonas J Gomez Nicolas Oswaldo NO van Ham Marco M Jänsch Lothar L Kalesse Markus M Pich Andreas A Brönstrup Mark M Häussler Susanne S Blankenfeldt Wulf W

Nature communications 20221201 1

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 wit ...[more]

PMID: 36456567

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Project description:Quorum-sensing (QS) is a cell-cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. While the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of and response to complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (non-additive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa, and demonstrate significant differences in signal decay between its two primary signal molecules as well as diverse combinatorial responses to dual signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic M-bM-^@M-^XAND-gateM-bM-^@M-^Y responses to multiple signal inputs, ensuring the effective expression of secreted factors in high density and low mass-transfer environments. Our results support a novel functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication. The two primary signal molecules of P. aeruginosa are the homoserine lactones N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) and N-butyryl-homoserine lactone (C4-HSL). Effects of the different signal molecules was assessed using a double QS synthase mutant of Pseudomonas aeruginosa PAO1 lasI/rhlI grown at 37M-BM-0C in 25 ml LB broth and 250 ml flasks with shaking at 200 r.p.m. in four treatments, each with a replicate: (a) no addition; (b) 3-oxo- C12-HSL; (c) C4-HSL; and (d) both 3-oxo-C12-HSL and C4-HSL.