Chloramphenicol CM resistance in staphylococci is increased after prior treatment with subinhibitory concentrations of CM. The resistance of induced population was decreased when cultured in drug-free media. Enhancement of CM-resistance after induction is accounted for by the increase in the formation of CM-acetyltransferase. Antibacterial activity of 16 CM-derivatives and analogues and their induction ability for CM-resistance were examined. It was found that CM16, CM17 and CM18 could not induce CM-resistance under the conditions used, but have much higher antibacterial activity than that of CM. It was found that prior treatment with subinhibitory concentrations of TC enhanced the level of TC-resistance. CM, actinomycin D and histidine deprivation in his-auxotroph inhibit the induction for TC-resistance. We have isolated a mutant in which leucomycin LM is active inducer for Mac resistance. Antibacterial and inducer activities of LM and its derivatives were examined. Mechanisms of Mac-resistance after induction was investigated. It was found that EM-binding to ribosomes was decreased after induction. 14C-phenylalanine was incorporated into protein in cell-free system of the combination of ribosomes from S.aureus and supernatant of E.coli. The ribosomes decrease their binding to spiramycin SP in parallel with the increase in resistance levels to SP and accordingly, the inhibition of polypeptide synthesis by SP in Mac-inducible resistant strain. Author
Rept. no. 3 (Final), 1 Sep 68-25 Mar 69,
Prepared in cooperation with Gunma Univ., Maebashi (Japan). Dept. of Microbiology.