Publications by authors named "Michelle F Homsher"
Article Synopsis
- A multidrug-resistant Gram-negative bacterium is causing serious infections and poses a growing health threat, making new treatment options essential.
- Researchers are focusing on inhibiting the MsbA transporter, which is crucial for the bacterium's survival.
- They optimized a compound known as cerastecin D, which showed promising antibacterial activity and effectiveness in mouse models for treating infections.
The development of new antimicrobial drugs is a priority to combat the increasing spread of multidrug-resistant bacteria. This development is especially problematic in gram-negative bacteria due to the outer membrane (OM) permeability barrier and multidrug efflux pumps. Therefore, we screened for compounds that target essential, nonredundant, surface-exposed processes in gram-negative bacteria.
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- * To streamline this process, researchers can start with a smaller subset of compounds and use virtual screening methods to prioritize which additional compounds to test, combining multiple screening techniques for better results.
- * A new method of combining these prioritizations was tested and showed to retrieve significantly more active compounds compared to using a single approach, improving the efficiency of drug discovery and guiding future screening strategies.
Agonist shift assays feature cross-titrations of allosteric modulators and orthosteric ligands. Information generated in agonist shift assays can include a modulator's effect on the orthosteric agonist's potency (alpha) and efficacy (beta), as well as direct agonist activity of the allosteric ligand (tauB) and the intrinsic binding affinity of the modulator to the unoccupied receptor (KB). Because of the heavy resource demand and complex data handling, these allosteric parameters are determined infrequently during the course of a drug discovery program and on a relatively small subset of compounds.
View Article and Find Full Text PDFAutomated mechanism of action studies are introducing the need for tailored compound delivery, which can be challenging for standard compound management procedures. Jump dilution assays investigating inhibitor reversibility require compound delivery at specific volumes to assay specific concentrations of 10 × IC for each inhibitor. Creating custom-made source plates with unique compound concentrations to dispense a uniform single volume can be prohibitively slow.
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