Accumulation in gram-postive and gram-negative bacteria as a mechanism of resistance to erythromycin.
Erythromycin was recovered in high yield after incubation with gram-negative bacteria. The cell-free protein-synthesizing preparation from gram-negative bacteria is equally as susceptible to the antibiotic as is that from gram-positive bacteria. Thus, neither destruction of erythromycin nor the absence of the step susceptible to the antibiotic plays an important role in the resistance mechanism of gram-negative bacteria. A 100-fold difference in accumulation of erythromycin between gram-positive and gram-negative bacteria was observed. This alone explains the resistance of gram-negative bacteria to erythromycin. Furthermore, data showed that the inhibition of growth is closely related to the accumulation of erythromycin. The concentration of intracellular erythromycin in gram-positive bacteria was found to be 44- to 90-fold greater than that of the extracellular medium. However, the antibiotic did not accumulate on the cell walls, nor was the accumulation energy-dependent. It is proposed that it takes place by the binding of erythromycin to the bacterial ribosomes, forming a very stable complex. The dissociation constants of erythromycin-Staphylococcus aureus complex and erythromycin-Bacillus subtilis complex were determined to be 1.1 x 10(-7) and 3.4 x 11(-7)m, respectively.
D001386:Azides / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects*; D002247:Carbon Isotopes; D002473:Cell Wall / Q000378:metabolism; D003486:Cyanides / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D006358:Hot Temperature; D010452:Peptide Biosynthesis; D011511:Proteus / Q000187:drug effects*; D012270:Ribosomes / Q000378:metabolism; D013210:Staphylococcus / Q000187:drug effects*
D001386:Azides; D002247:Carbon Isotopes; D003486:Cyanides; D004140:Dinitrophenols; D004917:Erythromycin