Our novel findings demonstrate that L. monocytogenes glutaredoxin plays a counterintuitive role in bacterial oxidative resistance and intracellular infection, lack of Grx remarkably rendered L. monocytogenes more tolerant to the oxidizing environment, and more importantly, rendered this pathogen more efficient to invade and cell-to-cell spread during infection on host cells and mice model. Here, GLRX is linked to infection.