Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa

R. E.W. Hancock, V. J. Raffle, T. I. Nicas

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Abstract

Induction of a major outer membrane protein, H1, in P. aeruginosa resulted in decreased susceptibility to gentamicin and streptomycin. Mutants which overproduce protein H1 and cells in which H1 is induced in response to growth conditions had altered kinetics of uptake and killing. It was further demonstrated that gentamicin and streptomycin interact with the outer membrane to permeabilize it to lysozyme and to increase the permeation of a chromogenic β-lactam, nitrocefin. Experiments with inhibitors of aminoglycoside uptake showed that uptake was not required to increase permeability. Mg2+ at 1 mM totally inhibited aminoglycoside-mediated outer membrane permeabilization. It is proposed that the uptake and killing by these aminoglycosides requires interaction with an Mg2+ binding site at the outer membrane, permitting aminoglycoside uptake into the periplasm.

Original languageEnglish
Pages (from-to)777-785
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume19
Issue number5
DOIs
Publication statusPublished - 1 Jan 1981
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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