Molecular Pharmacology, Vol 3, 586-594, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

Adaptation of Populations of Bacillus cereus to Tetracycline

¹ Department of Pharmacology, The George Washington University School of Medicine, Washington, D.C. 20005, and Department of Moleculor Biology, Walter Reed Army Institute of Research, Washington, D.C.

After initial inhibition by tetracycline at concentrations from 10^-6 to 10^-5 M, populations of Bacillus cereus in a casein hydrolyzate-salts medium resumed exponential growth. Sensitivity to the antibiotic was reestablished by time bacteria upon continued growth in the absence of tetracycline; restoring the antibiotic to such sensitive cultures resulted in a second emergence of resistance. Tetracycline was not significantly inactivated by the bacteria.

B. cereus accumulated tetracycline, and maximal intracellular concentrations were attained within approximately 20 min. The organisms escaped from the action of the drug by eliminating tetracycline progressively until the intracellular concentration of the antibiotic was no longer sufficient to sustain growth inhibition. The rate of egress of tetracycline from B. cereus was linear. Increasing the Mg²⁺ or Ca²⁺ concentrations or the pH of the medium resulted in the accumulation of lower levels of tetracycline by time cells but was without influence on the rate of egress of the drug.

B. cereus did not eliminate tetracycline at 2° or in media that either were devoid of amino acids or contained arsenite (10^-3 M).

Ribosomal 30 S subunits from adapted or nonadapted B. cereus bound similar quantities of tetracycline-7-³H upon centrifugation into sucrose gradients.

Note:
ACKNOWLEDGMENTS This investigation was supported by USPHS Research Grant AI-04264 from time National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.