Chemical and biomolecular insights into the agr quorum sensing system: Current progress and ongoing challenges.

is a ubiquitous bacterium that has become a major threat to human health due to its extensive toxin production and tremendous capacity for antibiotic resistance (e.g., MRSA "superbug" infections).

Characterization of an Autoinducing Peptide Signal Reveals Highly Efficacious Synthetic Inhibitors and Activators of Quorum Sensing and Biofilm Formation in .

Bacteria can use chemical signals to assess their local population density in a process called quorum sensing (QS). Many of these bacteria are common pathogens, including Gram-positive bacteria that utilize QS systems regulated by macrocyclic autoinducing peptide (AIP) signals. , an important foodborne pathogen, uses an system to regulate a variety of virulence factors and biofilm formation, yet little is known about the specific roles of in infection and its persistence in various environments.

Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. There are no drugs indicated for the core impairments of ASD.

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A synthetic peptide was found to block cell-to-cell signalling, or quorum sensing, in bacteria and be highly bioavailable in mouse tissue. The controlled release of this agent from degradable polymeric microparticles strongly inhibited skin infection in a wound model at levels that far surpassed the potency of the peptide when delivered conventionally.

Non-Native Peptides Capable of Pan-Activating the Quorum Sensing System across Multiple Specificity Groups of .

is a leading cause of hospital-acquired infections. Traditional antibiotics have significantly reduced efficacy against this pathogen due to its ability to form biofilms on abiotic surfaces and drug resistance. The accessory gene regulator () quorum sensing system is directly involved in pathogenesis.

Chemical Control of Quorum Sensing in : Identification of Small Molecule Modulators of SdiA and Mechanistic Characterization of a Covalent Inhibitor.

Enterohemorrhagic (EHEC) is the causative agent of severe diarrheal disease in humans. Cattle are the natural reservoir of EHEC, and approximately 75% of EHEC infections in humans stem from bovine products. Many common bacterial pathogens, including EHEC, rely on chemical communication systems, such as quorum sensing (QS), to regulate virulence and facilitate host colonization.

Conformational Switch to a β-Turn in a Staphylococcal Quorum Sensing Signal Peptide Causes a Dramatic Increase in Potency.

We report the solution-phase structures of native signal peptides and related analogs capable of either strongly agonizing or antagonizing the AgrC quorum sensing (QS) receptor in the emerging pathogen . Chronic infections are often recalcitrant to traditional therapies due to antibiotic resistance and formation of robust biofilms. The accessory gene regulator () QS system plays an important role in biofilm formation in this opportunistic pathogen, and the binding of an autoinducing peptide (AIP) signal to its cognate transmembrane receptor (AgrC) is responsible for controlling .

Re-refinement of Plasmodium falciparum orotidine 5'-monophosphate decarboxylase provides a clearer picture of an important malarial drug target.

The development of antimalarial drugs remains a public health priority, and the orotidine 5'-monophosphate decarboxylase from Plasmodium falciparum (PfOMPDC) has great potential as a drug target. The crystallization of PfOMPDC with substrate bound represents an important advance for structure-based drug-design efforts [Tokuoka et al. (2008), J.

Marine Biodiscovery Goes Deeper: Using In Vivo Bioassays Based on Model Organisms to Identify Biomedically Relevant Marine Metabolites.

Secondary metabolites from marine organisms are structurally diverse small molecules with high levels of bioactivity, and represent an underutilized resource for modern drug discovery. To facilitate the identification of drug-like marine metabolites, the significant potential of in vivo models of human disease - in particular those suitable for medium-throughput screening and bioassay-guided fractionation - should be explored in future marine biodiscovery efforts. Here, we explore the advantages of Caenorhabditis elegans, Drosophila, and zebrafish bioassays for marine biodiscovery, and review recent progress in using these in vivo models to identify bioactive marine metabolites.