Abstract: | The surge in drug‐resistant bacterial infections threatens to overburden healthcare systems worldwide. Bacterial cell walls are essential to bacteria, thus making them unique targets for the development of antibiotics. We describe a cellular reporter to directly monitor the phenotypic switch in drug‐resistant bacteria with temporal resolution. Vancomycin‐resistant enterococci (VRE) escape the bactericidal action of vancomycin by chemically modifying their cell‐wall precursors. A synthetic cell‐wall analogue was developed to hijack the biosynthetic rewiring of drug‐resistant cells in response to antibiotics. Our study provides the first in vivo VanX reporter agent that responds to cell‐wall alteration in drug‐resistant bacteria. Cellular reporters that reveal mechanisms related to antibiotic resistance can potentially have a significant impact on the fundamental understanding of cellular adaption to antibiotics. |