Effects of production of abnormal proteins on the rate of killing of Escherichia coli by streptomycin.
The role of abnormal membrane proteins in modulating the rate of killing by streptomycin was investigated. Davis et al. (B.D. Davis, L. Chen, and P.T. Tai, Proc. Natl. Acad. Sci. USA 83:6164-6168, 1986) have proposed that misread membrane proteins created by the action of streptomycin on translating ribosomes cause the formation of nonspecific membrane channels which allow increased uptake of the antibiotic and contribute to its bactericidal action. Pretreatment of Escherichia coli with a low concentration of puromycin enhanced the rate of killing by streptomycin. The effect of the pretreatment with puromycin was transient, since approximately normal rates of killing by streptomycin were restored after 30 min of incubation in antibiotic-free medium. This time period correlates with the time required to degrade labile polypeptides in puromycin-treated cells. The induction of a specific abnormal malE-lacZ fusion protein, which is capable of disrupting the normal membrane protein secretion process, also increased the rate of killing by streptomycin. Induction of malF-phoA fusion proteins, which have no significant effects on membrane integrity, did not alter susceptibility to streptomycin. These observations suggest that certain abnormal membrane proteins can contribute to the bactericidal action of streptomycin.
Department of Biological Sciences, Nelson Biological Laboratories, Rutgers University, Piscataway, New Jersey 08855-1059.
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D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects*; D008561:Membrane Fusion / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011691:Puromycin / Q000494:pharmacology*; D013307:Streptomycin / Q000494:pharmacology*
D008565:Membrane Proteins; D011691:Puromycin; D013307:Streptomycin