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Staphylococcus aureus uses small peptides to assess its population densisty ( i.e. , quorum sensing) and regulate virulence at high cell number. Here, we report the design and synthesis of peptidomimetics based on these native signals that strongly block this communication pathway in all four specificity groups of S. aureus . 

Abstract We used deep-learning-based models to automatically obtain elastic moduli from resonant ultrasound spectroscopy (RUS) spectra, which conventionally require user intervention of published analysis codes. By strategically converting theoretical RUS spectra into their modulated fingerprints and using them as a dataset to train neural network models, we obtained models that successfully predicted both elastic moduli from theoretical test spectra of an isotropic material and from a measured steel RUS spectrum with up to 9.6% missing resonances. We further trained modulated fingerprint-based models to resolve RUS spectra from yttrium–aluminum-garnet (YAG) ceramic samples with three elastic moduli. The resulting models were capable of retrieving all three elastic moduli from spectra with a maximum of 26% missing frequencies. In summary, our modulated fingerprint method is an efficient tool to transform raw spectroscopy data and train neural network models with high accuracy and resistance to spectra distortion. 

Abstract Staphylococcus aureusis 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). Amid a worsening antibiotic resistance crisis, new strategies to combat this deadly microbe that remove the selective pressure of traditional approaches are in high demand.S. aureusutilizes an accessory gene regulator (agr) quorum sensing network to monitor its local cellular population and trigger a devastating communal attack, like an invading horde, once a threshold cell density has been reached. The role of theagrsystem in a range of disease types is still being unraveled. Herein, we discuss the present‐day biochemical understanding ofagralong with unresolved details, describe its connection to the progression of infection, and review how chemical strategies have been implemented to study and intercept this signaling pathway. This research is illuminating the potential ofagras an anti‐virulence target inS. aureusand should inform the study of similar, yet less studied,agrsystems in related bacterial pathogens. 

Abstract A gold(I)‐catalyzed enantioselective dearomatization is achieved via metal‐chiral ligand cooperation. A new and divergent synthesis of chiral bifunctional binaphthyl‐2‐ylphosphines is developed to allow rapid access to these ligands, which in turn facilitate the application of this chemistry to a broad substrate scope including 1‐naphthols, 2‐naphthols, and phenols. Enantiomeric excesses up to 98 % are achieved via selective acceleration of one enantiomer formation enabled by hydrogen bonding between substrate and ligand remote basic group. DFT calculations lend support to the cooperative catalysis and substantiate the reaction stereochemical outcomes. 

Abstract There is significant interest in approaches to the treatment of bacterial infections that block virulence without creating selective pressures that lead to resistance. Here, we report the development of an “anti‐virulence” strategy that exploits the activity of potent synthetic inhibitors of quorum sensing (QS) inStaphylococcus aureus. We identify peptide‐based inhibitors of QS that are resistant to sequestration or degradation by components of murine tissue and demonstrate that encapsulation of a lead inhibitor in degradable polymer microparticles provides materials that substantially inhibit QSin vitro. Using a murine abscess model, we show that this inhibitor attenuates methicillin‐resistantS. aureus(MRSA) skin infectionsin vivo, and that sustained release of the inhibitor from microparticles significantly improved outcomes compared to mice that received a single‐dose bolus. Our results present an effective and modular approach to controlling bacterial virulencein vivoand could advance the development of new strategies for skin infection control.