Reversible signal binding by the Pseudomonas aeruginosa quorum-sensing signal receptor LasR.

Many members of the LuxR family of acyl-homoserine lactone (acyl-HSL)-dependent quorum-sensing transcriptional activators are thought to have the unusual characteristics of requiring the signal ligand during polypeptide synthesis to fold into an active conformation and of binding signal extraordinarily tightly. This is the case for the N-3-oxo-dodecanoyl-HSL-dependent Pseudomonas aeruginosa virulence regulator LasR. We present evidence that LasR can fold into an active conformation in vivo in the absence of the acyl-HSL ligand.

Calprotectin S100A9 calcium-binding loops I and II are essential for keratinocyte resistance to bacterial invasion.

Epithelial cells expressing calprotectin, a heterodimer of S100A8 and S100A9 proteins, are more resistant to bacterial invasion. To determine structural motifs that affect resistance to bacterial invasion, mutations were constructed in S100A9 targeting the calcium-binding loops I and II (E36Q, E78Q, E36Q,E78Q) and the C terminus (S100A9(1-99) and S100A9(1-112)), which contains putative antimicrobial zinc-binding and phosphorylation sites. The S100A8 and mutated S100A9 encoding plasmids were transfected into calprotectin-negative KB carcinoma cells.

Synthetic ligands that activate and inhibit a quorum-sensing regulator in Pseudomonas aeruginosa.

The transcription factor QscR is a regulator of quorum sensing in Pseudomonas aeruginosa and plays a role in controlling virulence in this prevalent opportunistic pathogen. This study outlines the discovery of a set of synthetic N-acylated homoserine lactones that are capable of either activating or strongly inhibiting QscR in a cell-based reporter gene assay. We demonstrate that the synthetic antagonists inhibit ligand-dependent QscR binding to DNA.