[Characteristics of mutants of Streptomyces peucetius subsp. caesius ATCC 27952 resistant to anthracycline antibiotics].
Daunorubicine (DNR) and doxorubicine (DXR) resistance to anthracycline antibiotics and antibiotical activity of the strain Streptomyces peucetius subsp. caesius ATCC 27952-2 and its daunorubicine- and doxorubicine-resistant (DNRr and DXRr) mutants have been studied. It has been found that strain S. peucetius subsp. caesius ATCC 27952-2 is much more resistant to DXR than to DNR. It has been shown that frequency of appearance of spontaneous mutants of the strain S. peucetius subsp. caesius ATCC 27952-2, resistant to DNR (10-30 micrograms/ml) makes 1.1 x 10(-6)-1.0 x 10(-8) and DXR (10-30 micrograms/ml) 7.7 x 10(-4)-3.0 x 10(-4). Treatment of spores of the initial strain by N-methyl-N'-nitro-N-nitrosoguanidin resulted in the 60-700-fold increase of arising frequency of DNRr-mutants while frequency of arising of DXRr-mutants did not change essentially. The majority of DNRr-mutants (76.9%) were characterised by high resistance to DXR, while there are such mutants among DXRr-mutants which possess the cross-resistance to DNR (below 30%). The mean value of antibiotic activity was the highest among DXRr-mutants induced by NG and sampled in the medium with 30 micrograms/ml of DXR. The majority of the tested DNRr- and DXRr-mutants (13 of 15) synthesized 1.8-10.9 times more of anthracycline compounds as compared with the initial strain. All the mutants synthesized 2.6-28.3 and 1.6-20.7 times more of DNR and DXR, respectively, than the initial strain. The results obtained prove that it is expedient to search for the strains with high production of DXR among DNR1-mutants, while DXRr-mutants are promising for choosing the producers of the both antibiotics.
Dubyts'ka
L P
LP
Ivan Franko Lviv National University.
Fedorenko
V O
VO
D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis / Q000494:pharmacology*; D003470:Culture Media; D003630:Daunorubicin / Q000096:biosynthesis / Q000494:pharmacology; D004317:Doxorubicin / Q000096:biosynthesis / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D016296:Mutagenesis / Q000187:drug effects; D009154:Mutation; D013171:Spores, Bacterial / Q000187:drug effects; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D008769:Methylnitronitrosoguanidine; D004317:Doxorubicin; D003630:Daunorubicin