Outer-membrane penetration barriers as components of intrinsic resistance to beta-lactam and other antibiotics in Escherichia coli K-12.
A new technique has been devised to investigate the penetration of antibiotics through the gram-negative outer membrane; the application here was to study intrinsic resistance of Escherichia coli K-12. Exponential cells in broth were briefly treated with 2.5 mM ethylenediaminetetraacetic acid at 5 degrees C to disrupt the outer membrane penetration barrier, and the response of treated and untreated cells to antibiotics was compared by turbidimetry. A barrier index was derived to describe the ability of 7 beta-lactam and 10 other antibiotics to penetrate the outer membrane of strain Y10. There was correlation between the molecular weight and log(10) barrier index (r = 0.59, P congruent with 0.01). The envelope mutant D22 (envA) had low barrier indexes for erythromycin, rifampin, ampicillin, and cloxacillin. For the beta-lactams, outer membrane penetration and affinity for inner membrane target site(s) triggering cell lysis were measured as independent components of the overall activity; although penetration and overall activity varied greatly, the affinities of most were within a narrow range.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D003470:Culture Media; D004352:Drug Resistance, Microbial; D004492:Edetic Acid / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure*; D005613:Freeze Etching; D009113:Muramidase / Q000494:pharmacology; D013997:Time Factors; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D003470:Culture Media; D047090:beta-Lactams; D004492:Edetic Acid; D009113:Muramidase