l-Serine potentiates fluoroquinolone activity against<i>Escherichia coli</i>by enhancing endogenous reactive oxygen species production

BACKGROUND: The increase in multiple antimicrobial-resistant bacteria seriously threatens global public health. Novel effective strategies are urgently needed. l-Serine was reported as the most effective amino acid inhibitor against bacterial growth and can sensitize Escherichia coli cells to gentamicin. It is currently unknown whether l-serine affects other type of antibiotics such as β-lactams and fluoroquinolones. METHODS: Using E. coli, we studied the combination of l-serine with diverse antibiotics against laboratory and clinical E. coli cultures and persisters. The intracellular NAD(+)/NADH level and ROS were determined using kits. Total cellular iron was determined by using a colorimetric ferrozine-based assay. RESULTS: Exogenous l-serine sensitized E. coli ATCC 25922 and clinically isolated fluoroquinolone-resistant E. coli to fluoroquinolones. This potentiation is independent of growth…