ABSTRACT
Introduction ........................................................................................................ 170 What Do We Mean by Permeability? ................................................................ 170 Permeability Barriers of the Bacterial Cell ....................................................... 171
Structure of Bacterial Cell Envelopes .................................................... 171 Envelope Components Relevant to Antibiotic Permeability .................. 172
Self-Induced Uptake of Aminoglycoside Antibiotics through the Outer Membrane of Gram-Negative Bacteria ................................................... 173
Resistance Associated with Species-Specifi c Variations and Mutational Alteration in Envelope Structure ............................................................ 173
Illicit Uptake: The Use of Metabolic Uptake Systems for Antibiotic Entry ..... 174 Energy-Dependent Uptake of Antibiotics and Resistance Arising from
Compromise of Energy Metabolism ....................................................... 176 Modifi cation of Uptake by Administration of a Second Agent ......................... 177 Effects of Biofi lm Formation on Antibiotic Permeation ................................... 178 Overcoming Resistance Associated with Permeability Barriers ....................... 179 References .......................................................................................................... 179
The ability of antimicrobial compounds to enter bacterial cells generally is a prerequisite to their antibacterial action. In order to penetrate the outer layers of the cell-the cell envelope-semi-permeable membranes and polymeric cell wall structures must be negotiated. Depending on the chemical nature of the antibiotic (hydrophilic or hydrophobic), penetration may occur by use of transmembrane pores, by localized disorganization of the membrane, by diffusion through the lipid bilayer, or by transport processes involving the co-opting of nutrient transport systems. Bacterial species differ widely in their envelope structures, and hence in their intrinsic resistance to antibiotics.
