Breaching the Barrier: Quantifying Antibiotic Permeability across Gram-negative Bacterial Membranes.

摘要: The double-membrane cell envelope of Gram-negative bacteria is a sophisticated barrier that facilitates the uptake nutrients and protects organism from toxic compounds. An antibiotic molecule must find its way through negatively charged lipopolysaccharide layer on outer surface, pass either porin or hydrophobic membrane, then traverse hydrophilic peptidoglycan only to another lipid bilayer before it finally enters cytoplasm, where typically finds target. This complex pathway with very different physico-chemical properties one reason are intrinsically protected against multiple classes antibiotic-like molecules, likely main in vitro target-based screening programs have failed deliver novel antibiotics for these organisms. Due lack general methods available quantifying flux drugs into cell, little known about permeation rates, transport pathways accumulation at target sites particular molecules. Here we summarize current tools measuring across compartments bacteria.