title: Penetration through the gram-negative cell wall: a co-determinant of the efficacy of beta-lactam antibiotics.
abstract: Resistance of gram-negative bacteria to beta-lactam antibiotics is based mainly on two mechanisms: hydrolysis by beta-lactamases and exclusion of the antibiotics from their target sites in the inner membrane. This article describes the use of Pseudomonas aeruginosa K 799/WT and a mutant of this strain (K 799/61) to assess the role of the outer membrane as a permeability barrier to penicillins and cephalosporins. The data confirm the importance of good penetration for a beta-lactam to be active against Pseudomonas. The second part illustrates the interplay of beta-lactamases and the outer membrane in the resistance of Escherichia coli to beta-lactams. A method to determine membrane permeability parameters parameters is given. The results support the idea that only a combined consideration of inactivating enzymes and penetration barriers can lead to a better understanding of the efficiency of the defence mechanisms which gram-negative bacteria can invoke against beta-lactam antibiotics.
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D002473:Cell Wall / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases