Magnesium modulates phospholipid metabolism to promote bacterial phenotypic resistance to antibiotics

Non-inheritable antibiotic resistance or phenotypic resistance ensures bacterial survival upon antibiotic treatment. However, exogenous factors in promoting phenotypic resistance is poorly defined. Here, we demonstrate that Vibrio alginolyticus are recalcitrant to killing by a broad spectrum of antibiotics under high magnesium. Functional metabolomics demonstrate that magnetism modulates the biosynthesis of fatty acids in increasing the biosynthesis of saturated fatty acids while decreasing unsaturated fatty acids. Exogenous supplementation of fatty acids confirm the role of fatty acids in antibiotic resistance. Furthermore, functional lipidomics reveal that glycerophospholipid metabolism is the major metabolic pathway remodeled by magnetism, where the biosynthesis of PE is decreased but PG is increased. Thus, the membrane composition is altered, leading to increased membrane polarization, and decreased permeability and fluidity. These together reduce the uptake of antibiotics by the bacteria. Thus, our study suggest a previously unrecognized metabolic mechanism by which bacteria escape antibiotic killing by utilizing environmental factor.