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Inhibition of growth and RNA biosynthesis of Bacillus cereus by quinacrine.

Summary: The addition of 0.4 mM-quinacrine to exponential cultures of Bacillus cereus led to the complete inhibition of growth, measured turbidimetrically. Certain metal ions such as Ca2+ and Mg2+ were partially effective in preventing growth inhibition, as was the polyamine spermine. Quinacrine inhibited most biosynthetic processes measured to the same extent as the reduction in the rate of growth. Thus the incorporation of amino acids into protein, that of diaminopimelic acid into bacterial wall, the accumulation of K+ and the uptake of nicotinic acid were diminished only in accordance with the decreased rate of turbidimetric increase. DNA biosynthesis was decreased to a lesser extent than was turbidity and continued even after growth had ceased altogether, thus indicating less inhibition of this process than that of protein formation. RNA synthesis, on the other hand, was selectively inhibited in these cells. The depressant effect was most pronounced when ribosomal or rRNA formation was examined. RNA isolated from drug-treated cells still exhibited messenger function. An additional effect of quinacrine on the uptake of certain nucleic acid bases is also postulated. The relative content of ATP in the cells was considerably increased by drug treatment. It appears that quinacrine did not exert its major action on DNA biosynthesis but selectively blocked RNA formation while that of DNA was permitted to continue.