title: Early cell envelope alterations by tobramycin associated with its lethal action on Pseudomonas aeruginosa.
abstract: The immediate activities of the aminoglycoside antibiotic tobramycin were investigated in Pseudomonas aeruginosa PAO1. The lethal action of a low concentration of tobramycin (8 micrograms ml-1) occurred rapidly (1-3 min) and was associated with leakage of certain cellular components into the supernatant. The presence of magnesium at the time of initial exposure protected cells by preventing uptake of tobramycin; however, magnesium addition following a brief exposure did not restore viability. Analyses of supernatant material revealed a rapid 2-fold increase in protein released following tobramycin treatment. A prominent 29 kDa protein, observed by SDS-PAGE in the released material was identified as the periplasmic beta-lactamase. Brief exposure to tobramycin did not result in major morphological damage or cell lysis as observed by transmission electron microscopy, and release of LPS was not a primary event. Although activity at the ribosomal level was observed by 2-3 min, leakage was detected after only 1 min. These data indicate that leakage of cellular components, particularly beta-lactamase, occurs simultaneously, if not prior to inhibition of protein synthesis by tobramycin.
authors.affiliation: Department of Biochemistry, University of North Carolina, Chapel Hill 27599-7260.
authors.forename: J E
authors.initials: JE
authors.lastname: Raulston
authors.forename: T C
authors.initials: TC
authors.lastname: Montie
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D008854:Microscopy, Electron; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D014031:Tobramycin / Q000493:pharmacokinetics / Q000494:pharmacology*; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; D014031:Tobramycin