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Las/Rhl cell signaling system

Responsible: Robert Cool, Alicia Allen, and Erin Feeney

Las System

Signal Molecule: An AHL called PAI-1 (N-3-oxododecanoyl-l-hsl)(3-oxo-C12-hsl)

Bacterial species: Pseudomonas aeruginosa gram(-) possibly E.coli (see article 3)

Receiver protein: LasR

Effect of binding: TXN activation of virulence genes, lasA, lasB, apr, toxR

Synthase: LasI enzyme

Target Genes: lasI, lasA, lasB, apr, toxR

Regulation: unknown

References

"Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of elastase and rhamnolipid biosynthesis genes"

JP Pearson, EC Pesci and BH Iglewski [1]

"Regulation of Pseudomonas Quinolone Signal Synthesis in Pseudomonas aeruginosa"

Dana S. Wade, M. Worth Calfee, Edson R. Rocha, Elizabeth A. Ling, Elana Engstrom, James P. Coleman, and Everett C. Pesci 2

Posttranscriptional Control of Quorum-Sensing-Dependent Virulence Genes by DksA in Pseudomonas aeruginosa

Florence Jude,Thilo Köhler,Pavel Branny,Karl Perron,Matthias P. Mayer,Rachel Comte, and Christian van Delden 3

Pending: [2]

Rhl System

Signal Molecule: An AHL called PAI-2, Plasminogen activator inhibitor-2, N-butanoyl-homoserine lactone (C4HSL)

Bacterial species: Pseudomonas aeruginosa, gram(-)

Receiver Protein: Rhl R

Effect of Binding: activation of Rhamnosyl Transferase, then making RL (rhamnolipid)

Synthase: RhlA and RhlB

Target Genes: pqsABCDE and phnAB

Regulation: unknown

References

background information on Las and Rhl

Lux cell signaling system

Responsible: Andrew Gordon and Pallavi Penumetcha

Signal molecule: N-acyl-homoserine lactone (AHL) Generic term for a variety of species specific hormone-like molecules

Bacterial species: discovered in Vibrio fischeri known to work in E. coli

Receiver protein: LuxR protein receives signal from AHL; also has some control over transciption of luciferase

Signal molecule synthase: LuxI; also has some control over transciption of luciferase

Additional Information: "Quorum Quenching" aiiA (intracellular) lactonase reduces AHL concentration

Resources

Lux Operon Pathway

AHL signaling molecules by species; some are specific to gram pos but may affect gram negs

Reducing Crosstalk in Lux System

References

Quorum Quenching to control Lux Pathway

[3] A Synthetic multicellular system for programmed pattern formation

Lsr (AI-2) cell signaling system

Responsible: Kelly Davis, Xiao Zhu

Signal molecule: AI-2 (furanosyl borate diester in V. harveyi, a variety of other molecules in other species), all are derived from DPD. AI-2 is R-THMF in E. coli

[4]

Bacterial species:

lsrA,B,C,D,F,G,R,K: Escherichia coli HS, SMS-3-5, str. K12 substr. MG1655, and substr. DH10B.

lsrE:Escherichia coli str. K12 substr. MG1655

LuxS:Escherichia coli HS, SMS-3-5, APEC O1, str. K12 substr. MG1655, substr. DH10B, and UTI89.

Receiver protein: LsrR protein receives signal from sensor protein

Signal molecule synthase: Pfs enzyme, then LuxS autoinducer synthase

Target genes: lsr operon, including ABC transporter and LsrK kinase

Regulation: LsrR represses the lsr operon, derepression by phospho-AI-2; catabolite repression influences AI-2 accumulation through the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex, which directly stimulates transcription of the lsr operon and indirectly represses luxS expression.cAMP-CRP is shown to bind to a cAMP receptor protein (CRP) binding site located in the upstream region of the lsr promoter and works with the LsrR repressor to regulate AI-2 uptake.

Note: AI-2 is synthesized and secreted during exponential growth and is imported in stationary phase when glucose becomes limiting. In the presence of glucose, AI-2 is not imported because the lsr operon is not transcribed due to camp-CAP mediated repression. Both glycerol and G3P(glycerol 3-phosphate) repress lsr transcription, while the majority repression comes from G3P. DHAP represses lsr transcription by a cAMP-CAP-independent mechanism involving LsrR.

http://gcat.davidson.edu/GcatWiki/images/b/b8/N654260305_1291548_2335.jpg

Note:

lsrB encodes the periplasmic AI-2 binding protein

lsrC & lsrD encode the channel proteins

lsrA encodes the ATPase that provides energy for AI-2 transport

lsrF is similar to genes specifying aldolases

lsrG encodes a protein with an unknown function.

tam: trans-aconitate 2-methyltransferase, also known as lsrE or yneD yneE:conserved inner membrane protein

http://gcat.davidson.edu/GcatWiki/images/3/30/N654260305_1340817_550.jpg

R-THMF http://gcat.davidson.edu/GcatWiki/images/8/8c/S-DPD.gif http://www.nature.com/nrmicro/journal/v3/n5/images/nrmicro1146-f2.gif

http://gcat.davidson.edu/GcatWiki/images/c/c9/Grl.jpg

DHAP: dihydroxyacetone phosphate.

http://gcat.davidson.edu/GcatWiki/images/9/9b/Grlw.jpg

References

Cyclic AMP and cAMP Receptor Protein Influence both Synthesis and Uptake of Extracellular Autoinducer 2 in Escherichia coli

Global Effects of the Cell-to-Cell Signaling Molecules Autoinducer-2, Autoinducer-3, and Epinephrine in a luxS Mutant of Enterohemorrhagic Escherichia Coli

Shows how AI-2 is formed

Signaling explained with graphics of AI-2 pathways

Lsr-mediated transport and processing of AI-2 in Salmonella typhimurium

Review of AI-2 and other systems

Quorum Sensing in Escherichia coli Is Signaled by AI-2/LsrR: Effects on Small RNA and Biofilm Architecture

Regulation of Uptake and Processing of the Quorum-Sensing Autoinducer AI-2 in Escherichia coli

Resources

AI-2/DPD

alternate AI-2 synthesis

lsrK gene in Entrez

lsrR gene in Entrez

lsr nucleotide sequence in EcoCyc

Transcription of LuxS (interaction with micA,gshA)

http://gcat.davidson.edu/GcatWiki/images/c/cb/N654260305_1347432_6212.jpg