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α-Hydroxyketone synthesis and sensing by Legionella and Vibrio.

Tiaden A, Hilbi H - Sensors (Basel) (2012)

Bottom Line: AHK signaling regulates the virulence of L. pneumophila and V. cholerae, pathogen-host cell interactions, formation of biofilms or extracellular filaments, expression of a genomic "fitness island" and competence.Here, we outline the processes, wherein AHK signaling plays a role, and review recent insights into the function of proteins encoded by the lqs and cqs gene clusters.To this end, we will focus on the autoinducer synthases catalysing the biosynthesis of AHKs, on the cognate trans-membrane sensor kinases detecting the signals, and on components of the down-stream phosphorelay cascade that promote the transmission and integration of signaling events regulating gene expression.

View Article: PubMed Central - PubMed

Affiliation: Competence Center for Applied Biotechnology and Molecular Medicine, University Zürich, Zürich, Switzerland. nicki.tiaden@cabmm.uzh.ch

ABSTRACT
Bacteria synthesize and sense low molecular weight signaling molecules, termed autoinducers, to measure their population density and community complexity. One class of autoinducers, the α-hydroxyketones (AHKs), is produced and detected by the water-borne opportunistic pathogens Legionella pneumophila and Vibrio cholerae, which cause Legionnaires' disease and cholera, respectively. The "Legionella quorum sensing" (lqs) or "cholera quorum sensing" (cqs) genes encode enzymes that produce and sense the AHK molecules "Legionella autoinducer-1" (LAI-1; 3-hydroxypentadecane-4-one) or cholera autoinducer-1 (CAI-1; 3-hydroxytridecane-4-one). AHK signaling regulates the virulence of L. pneumophila and V. cholerae, pathogen-host cell interactions, formation of biofilms or extracellular filaments, expression of a genomic "fitness island" and competence. Here, we outline the processes, wherein AHK signaling plays a role, and review recent insights into the function of proteins encoded by the lqs and cqs gene clusters. To this end, we will focus on the autoinducer synthases catalysing the biosynthesis of AHKs, on the cognate trans-membrane sensor kinases detecting the signals, and on components of the down-stream phosphorelay cascade that promote the transmission and integration of signaling events regulating gene expression.

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Signal recognition by the V. cholerae CqsS and L. pneumophila LqsS sensor kinases. (a) Topology model of the V. cholerae CqsS trans-membrane sensor domain based on the secondary structure prediction algorithms TMPRED and TMHMM. The N-terminal sensor domain encompasses six trans-membrane α-helices and defines the specificity and sensitivity for distinct AHK molecules (enlarged circles, amino acid position and one-letter code). (b) Sensor domain regions (I, II, III) define the interactions with functional groups of AHK ligands. (I) TM 1–3 and periplasmic domain PD 1 contain conserved amino acid clusters essential for ligand binding and signal transduction (cytoplasmic domain CD 1). (II) TM 4 (W104, S107) discriminates between hydroxyl and amino groups at C3 of AHK ligands. (III) TM 6 (F162, C170) determines binding to the head group (methyl vs. phenyl) and the acyl tail of AHK ligands. (c) Amino acid sequence alignment (Clustal Omega algortithm) of the sensor domains of V. cholerae (V.ch) CqsS, V. harveyi (V.ha) CqsS and L. pneumophila (L.pn) LqsS. The positions of species-specific amino acids in the sensor domain regions (I, II, III) are indicated, and stars denote conserved amino acids. Color scheme: black (2/3 conserved); red (similar amino acids); grey (different amino acids); yellow (amino acids defining ligand sensitivity, specificity and signal transduction motifs); green (amino acid exchange results in altered ligand specificity). Boxes illustrate altered ligand preferences due to site-specific amino acid polymorphisms in sensor domain region II and III.
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f3-sensors-12-02899: Signal recognition by the V. cholerae CqsS and L. pneumophila LqsS sensor kinases. (a) Topology model of the V. cholerae CqsS trans-membrane sensor domain based on the secondary structure prediction algorithms TMPRED and TMHMM. The N-terminal sensor domain encompasses six trans-membrane α-helices and defines the specificity and sensitivity for distinct AHK molecules (enlarged circles, amino acid position and one-letter code). (b) Sensor domain regions (I, II, III) define the interactions with functional groups of AHK ligands. (I) TM 1–3 and periplasmic domain PD 1 contain conserved amino acid clusters essential for ligand binding and signal transduction (cytoplasmic domain CD 1). (II) TM 4 (W104, S107) discriminates between hydroxyl and amino groups at C3 of AHK ligands. (III) TM 6 (F162, C170) determines binding to the head group (methyl vs. phenyl) and the acyl tail of AHK ligands. (c) Amino acid sequence alignment (Clustal Omega algortithm) of the sensor domains of V. cholerae (V.ch) CqsS, V. harveyi (V.ha) CqsS and L. pneumophila (L.pn) LqsS. The positions of species-specific amino acids in the sensor domain regions (I, II, III) are indicated, and stars denote conserved amino acids. Color scheme: black (2/3 conserved); red (similar amino acids); grey (different amino acids); yellow (amino acids defining ligand sensitivity, specificity and signal transduction motifs); green (amino acid exchange results in altered ligand specificity). Boxes illustrate altered ligand preferences due to site-specific amino acid polymorphisms in sensor domain region II and III.

Mentions: The CAI-1 receptor CqsS and the potential LAI-1 receptor LqsS belong to the class of six trans-membrane helix TC sensor histidine kinases (Figure 3(a)). CqsS and LqsS couple the detection of the AI molecules via a receptor domain at the N-terminus to signal transduction modules at the C-terminal part of the protein [9]. TC sensor proteins are mainly located in the inner bacterial membrane, where they sense specific environmental signals present in the periplasmic space [62]. However, the molecular nature and the exact mechanisms of how these signals interact with the corresponding TC sensor kinases are poorly understood. Only a small fraction of TC system ligands has been identified so far, and therefore, AI molecules such as AHKs are valuable research tools to study membrane-bound sensors [3].


α-Hydroxyketone synthesis and sensing by Legionella and Vibrio.

Tiaden A, Hilbi H - Sensors (Basel) (2012)

Signal recognition by the V. cholerae CqsS and L. pneumophila LqsS sensor kinases. (a) Topology model of the V. cholerae CqsS trans-membrane sensor domain based on the secondary structure prediction algorithms TMPRED and TMHMM. The N-terminal sensor domain encompasses six trans-membrane α-helices and defines the specificity and sensitivity for distinct AHK molecules (enlarged circles, amino acid position and one-letter code). (b) Sensor domain regions (I, II, III) define the interactions with functional groups of AHK ligands. (I) TM 1–3 and periplasmic domain PD 1 contain conserved amino acid clusters essential for ligand binding and signal transduction (cytoplasmic domain CD 1). (II) TM 4 (W104, S107) discriminates between hydroxyl and amino groups at C3 of AHK ligands. (III) TM 6 (F162, C170) determines binding to the head group (methyl vs. phenyl) and the acyl tail of AHK ligands. (c) Amino acid sequence alignment (Clustal Omega algortithm) of the sensor domains of V. cholerae (V.ch) CqsS, V. harveyi (V.ha) CqsS and L. pneumophila (L.pn) LqsS. The positions of species-specific amino acids in the sensor domain regions (I, II, III) are indicated, and stars denote conserved amino acids. Color scheme: black (2/3 conserved); red (similar amino acids); grey (different amino acids); yellow (amino acids defining ligand sensitivity, specificity and signal transduction motifs); green (amino acid exchange results in altered ligand specificity). Boxes illustrate altered ligand preferences due to site-specific amino acid polymorphisms in sensor domain region II and III.
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f3-sensors-12-02899: Signal recognition by the V. cholerae CqsS and L. pneumophila LqsS sensor kinases. (a) Topology model of the V. cholerae CqsS trans-membrane sensor domain based on the secondary structure prediction algorithms TMPRED and TMHMM. The N-terminal sensor domain encompasses six trans-membrane α-helices and defines the specificity and sensitivity for distinct AHK molecules (enlarged circles, amino acid position and one-letter code). (b) Sensor domain regions (I, II, III) define the interactions with functional groups of AHK ligands. (I) TM 1–3 and periplasmic domain PD 1 contain conserved amino acid clusters essential for ligand binding and signal transduction (cytoplasmic domain CD 1). (II) TM 4 (W104, S107) discriminates between hydroxyl and amino groups at C3 of AHK ligands. (III) TM 6 (F162, C170) determines binding to the head group (methyl vs. phenyl) and the acyl tail of AHK ligands. (c) Amino acid sequence alignment (Clustal Omega algortithm) of the sensor domains of V. cholerae (V.ch) CqsS, V. harveyi (V.ha) CqsS and L. pneumophila (L.pn) LqsS. The positions of species-specific amino acids in the sensor domain regions (I, II, III) are indicated, and stars denote conserved amino acids. Color scheme: black (2/3 conserved); red (similar amino acids); grey (different amino acids); yellow (amino acids defining ligand sensitivity, specificity and signal transduction motifs); green (amino acid exchange results in altered ligand specificity). Boxes illustrate altered ligand preferences due to site-specific amino acid polymorphisms in sensor domain region II and III.
Mentions: The CAI-1 receptor CqsS and the potential LAI-1 receptor LqsS belong to the class of six trans-membrane helix TC sensor histidine kinases (Figure 3(a)). CqsS and LqsS couple the detection of the AI molecules via a receptor domain at the N-terminus to signal transduction modules at the C-terminal part of the protein [9]. TC sensor proteins are mainly located in the inner bacterial membrane, where they sense specific environmental signals present in the periplasmic space [62]. However, the molecular nature and the exact mechanisms of how these signals interact with the corresponding TC sensor kinases are poorly understood. Only a small fraction of TC system ligands has been identified so far, and therefore, AI molecules such as AHKs are valuable research tools to study membrane-bound sensors [3].

Bottom Line: AHK signaling regulates the virulence of L. pneumophila and V. cholerae, pathogen-host cell interactions, formation of biofilms or extracellular filaments, expression of a genomic "fitness island" and competence.Here, we outline the processes, wherein AHK signaling plays a role, and review recent insights into the function of proteins encoded by the lqs and cqs gene clusters.To this end, we will focus on the autoinducer synthases catalysing the biosynthesis of AHKs, on the cognate trans-membrane sensor kinases detecting the signals, and on components of the down-stream phosphorelay cascade that promote the transmission and integration of signaling events regulating gene expression.

View Article: PubMed Central - PubMed

Affiliation: Competence Center for Applied Biotechnology and Molecular Medicine, University Zürich, Zürich, Switzerland. nicki.tiaden@cabmm.uzh.ch

ABSTRACT
Bacteria synthesize and sense low molecular weight signaling molecules, termed autoinducers, to measure their population density and community complexity. One class of autoinducers, the α-hydroxyketones (AHKs), is produced and detected by the water-borne opportunistic pathogens Legionella pneumophila and Vibrio cholerae, which cause Legionnaires' disease and cholera, respectively. The "Legionella quorum sensing" (lqs) or "cholera quorum sensing" (cqs) genes encode enzymes that produce and sense the AHK molecules "Legionella autoinducer-1" (LAI-1; 3-hydroxypentadecane-4-one) or cholera autoinducer-1 (CAI-1; 3-hydroxytridecane-4-one). AHK signaling regulates the virulence of L. pneumophila and V. cholerae, pathogen-host cell interactions, formation of biofilms or extracellular filaments, expression of a genomic "fitness island" and competence. Here, we outline the processes, wherein AHK signaling plays a role, and review recent insights into the function of proteins encoded by the lqs and cqs gene clusters. To this end, we will focus on the autoinducer synthases catalysing the biosynthesis of AHKs, on the cognate trans-membrane sensor kinases detecting the signals, and on components of the down-stream phosphorelay cascade that promote the transmission and integration of signaling events regulating gene expression.

Show MeSH
Related in: MedlinePlus