L-lysine potentiates aminoglycosides against <i>Acinetobacter baumannii</i> via regulation of proton motive force and antibiotics uptake

<i>Acinetobacter baumannii</i>, a Gram-negative opportunistic pathogen, is a leading cause of hospital- and community-acquired infections. <i>Acinetobacter baumannii</i> can rapidly acquire diverse resistance mechanisms and undergo genetic modifications that confer resistance and persistence to all currently used clinical antibiotics. In this study, we found exogenous L-lysine sensitizes <i>Acinetobacter baumannii</i>, other Gram-negative bacteria (<i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>) and a Gram-positive bacterium (<i>Mycobacterium smegmatis</i>) to aminoglycosides. Importantly, the combination of L-lysine with aminoglycosides killed clinically isolated multidrug-resistant <i>Acinetobacter baumannii</i> and persister cells. The exogenous L-lysine can increase proton motive force via transmembrane chemical gradient, resulting in aminoglycoside acumination that further accounts for reactive oxygen species production. The combination of L-lysine and antibiotics highlights a promising strategy against bacterial infection.