Effect of Exogenous Glucose on Molecular Transport through Bacterial Membranes Studied by Second Harmonic Light Scattering

Recent studies revealed that exogenous glucose increases the efficacy of aminoglycosides in eliminating bacterial persister cells. It was speculated that this increased antimicrobial efficacy is induced by glucose-facilitated uptake of the antibiotics. Here, we examine this hypothesis by using second-harmonic light scattering to time-resolve the transport of an antimicrobial quaternary ammonium compound (QAC), malachite green, across the membranes of living <i>Escherichia coli</i> (<i>E. coli</i>) in the presence of glucose. The results show that when the glucose concentration increased from 0 to 100 μM, the QAC transport rate constant across the cytoplasmic membrane of <i>E. coli</i> increased by 3.6 times. Further increase of glucose concentration into the millimolar range, however, does not further enhance the transport rate constant. Conversely, a study of QAC transport across the protein-free membrane of liposomes (constructed from the polar lipid extract of <i>E. coli</i>) indicates that the glucose-induced enhancement in membrane transport in <i>E. coli</i> is mediated by protein transporters. Cell viability experiments show that low concentration of exogenous glucose enhances the QAC efficacy in eliminating <i>E. coli</i>. The loss of viability of the bacterial cells in the presence of the QAC at minimum inhibitory concentration increased dramatically when glucose concentration increased from 0 to 100 μM but increasing the glucose concentration up to 1 mM did not further enhance the antimicrobial efficacy. This behavior coincides with the observed increase in QAC transport rate constant as a function of glucose concentration. These observations reveal a novel antimicrobial strategy in which low concentration glucose enhances the uptake of antimicrobials into the bacteria, thereby improving antimicrobial efficacy.