The newly identified <i>grdA</i> gene confers high-level plazomicin resistance in <i>Salmonella enterica</i> serovars

Plazomicin, a next-generation aminoglycoside, was recently approved by the U.S. Food and Drug Administration for the treatment of multidrug-resistant complicated urinary tract infections. It is highly effective against most aminoglycoside-modifying enzymes (AMEs). Here, we report that <i>Salmonella enterica</i> strains containing the newly identified gentamicin resistance gene (<i>grdA</i>) are highly resistant to plazomicin. Heterologous expression of <i>grdA</i> in <i>Escherichia coli</i> Δ<i>tolC</i> resulted in plazomicin resistance with minimum inhibitory concentration (MIC) > 256 µg/mL. These findings reveal that GrdA confers significantly higher resistance to plazomicin than the previously known plazomicin-resistant AMEs AA (2)-Ia and APH (2″)-Iva.