Open AccessOuter-Membrane Penetration Barriers as Components of Intrinsic Resistance to Beta-Lactam and Other Antibiotics in Escherichia coli K-12
Author(s) -
R. A. Scudamore,
Terrance Beveridge,
M. Goldner
Publication year - 1979
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.15.2.182
Subject(s) - bacterial outer membrane , penetration (warfare) , escherichia coli , cell envelope , membrane , microbiology and biotechnology , chemistry , lysis , biophysics , turbidimetry , antibiotics , periplasmic space , polymyxin b , biology , chromatography , biochemistry , operations research , engineering , gene
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 ofEscherichia coli K-12. Exponential cells in broth were briefly treated with 2.5 mM ethylenediaminetetraacetic acid at 5°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 log10 barrier index (r = 0.59,P ≅ 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.