title: Physical methods to quantify small antibiotic molecules uptake into Gram-negative bacteria.
abstract: The development of antibiotics against Gram-negative bacteria is a challenge: any active compound must cross the outer cell envelope composed of a hydrophilic highly charged lipopolysaccharide layer followed by a tight hydrophobic layer containing water filled gates called porins to reach the hydrophilic periplasmic space and depending on the target with the further need to cross the hydrophobic inner membrane. In addition to a possible rapid enzymatic deactivation efflux pumps shuffle compounds back outside. The resulting low permeability of cell envelope requires high dose and leads therefore to toxicity problems. Despite its relevance the permeability barrier in Gram-negative bacteria is not well understood partially caused by the lack of appropriate direct assays. Here we give a brief introduction on current available techniques to quantify passive diffusion of small hydrophilic molecules into Gram-negative bacteria.
authors.affiliation: Jacobs University Bremen, Campusring 1, D-28759 Bremen, Germany. Electronic address: m.winterhalter@jacobs-university.de.
authors.forename: Mathias
authors.initials: M
authors.lastname: Winterhalter
authors.affiliation: Department of Physics, University of Cagliari, Cittadella Universitaria Monserrato, SP Monserrato-Sestu km 0.700, 09042 Monserrato, Italy. Electronic address: matteo.ceccarelli@dsf.unica.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ceccarelli
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004058:Diffusion; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism; D018272:Porins / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D018272:Porins
keywords: Antibiotics; Flux; Kinetics; Molecular modelling; Porins