Na + -NQR Confers Aminoglycoside Resistance via the Regulation of l- Alanine Metabolism

Abstract

The Na + -NQR complex functions as a unique redox-driven sodium pump, generating membrane potential directly. However, whether it mediates generation of membrane potential indirectly is unknown. The present study shows that the Na + -NQR complex impacts membrane potential through other antiporter families Atp and Mnh. It proceeds by ATP and then cAMP/CRP regulon, which inhibits l- alanine catabolism and promotes l- alanine anabolism. When the Na + -NQR complex is reduced as in antibiotic-resistant bacteria, l- alanine is depressed, which is related to the antibiotic resistance phenotypes. However, exogenous l- alanine reverts the phenotype and promotes antibiotic-mediated killing. These findings suggest a novel mechanism by which the Na + -NQR system regulates antibiotic resistance via l- alanine metabolism in a cAMP/CRP complex-dependent manner.