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Systematic Assessment of Accessibility to the Surface of Staphylococcus aureus
ACS Chemical Biology  (IF5.1),  Pub Date : 2021-10-05, DOI: 10.1021/acschembio.1c00604
Noel J. Ferraro, Seonghoon Kim, Wonpil Im, Marcos M. Pires

Proteins from bacterial foes, antimicrobial peptides, and host immune proteins must navigate past a dense layer of bacterial surface biomacromolecules to reach the peptidoglycan (PG) layer of Gram-positive bacteria. A subclass of molecules (e.g., antibiotics with intracellular targets) also must permeate through the PG (in a molecular sieving manner) to reach the cytoplasmic membrane. Despite the biological and therapeutic importance of surface accessibility, systematic analyses in live bacterial cells have been lacking. We describe a live cell fluorescence assay that is robust, shows a high level of reproducibility, and reports on the permeability of molecules to and within the PG scaffold. Moreover, our study shows that teichoic acids impede the permeability of molecules of a wide range of sizes and chemical composition.