![]() ![]() The transcription of genes involved in signaling molecule biosynthesis are also up-regulated hence, signaling molecules are often termed autoinducers. These signaling molecules diffuse between cells and once a critical threshold concentration has been reached, a specific receptor protein, which also acts as a transcriptional regulator, is activated, leading to a population-wide change in gene expression. ![]() 10–14 QS is mediated by small-molecular weight signaling molecules that are synthesized continually throughout growth and released into the surrounding media. 9Ī cell–cell signaling phenomenon known as quorum sensing (QS) enables bacteria to regulate gene transcription in a population cell density-dependent manner. 8 Such virulence factors include: tissue degrading enzymes, endotoxins, exotoxins, siderophores, organic molecules, and adherence components. 7 The pathogenicity of this Gram-negative bacterium is attributed to its ability to produce and secrete a large arsenal of virulence factors which are inimical to the physiology of the infected host. aeruginosa is also a major cause of mortality in cystic fibrosis (CF) patients, 5,6 and the incidence of multi-drug resistant strains is on the rise globally. It is responsible for many nosocomial infections, such as post-surgery infections, catheter associated infections, and ventilator associated pneumonia. ![]() Introduction Pseudomonas aeruginosa is a clinically relevant Gram-negative human pathogen that can cause acute or chronic infections, particularly in immunocompromised patients. This is the first indication of interaction between the Rhl and PQS systems at the protein/ligand level, which suggests that RhlR should be considered a highly attractive target for antivirulence strategies. Notably, we found evidence that PQS binds RhlR, the cognate receptor in the Rhl QS sub-system of P. Application of these probes led to the identification of previously unsuspected putative HHQ and PQS binders, thereby providing new insights into QS at a proteomic level and revealing potential new small molecule targets for virulence attenuation strategies. Herein, we report the development of HHQ and PQS photoaffinity-based probes for chemical proteomic studies. aeruginosa, and they are considered important factors in the progress of infections by this clinically relevant organism. The Pseudomonas Quinolone Signal (PQS) and 2-Heptyl-3 H-4-Quinolone (HHQ) are autoinducers in P. Many bacterial species, including the human pathogen Pseudomonas aeruginosa, employ a mechanism of intercellular communication known as quorum sensing (QS), which is mediated by signalling molecules termed autoinducers. ![]()
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