Multidrug resistant phenotype of Bacillus subtilis spontaneous mutants isolated in the presence of puromycin and lincomycin.
Spontaneous mutants were isolated by growing Bacillus subtilis 168 in the presence of high concentrations of puromycin and lincomycin. These mutants showed increased resistance to several drugs other than these two drugs. The ImrAB genes, which encode a transcriptional repressor and a drug efflux protein of the major facilitator superfamily, were involved in this phenotype. Northern hybridization analysis showed that the expression of ImrAB gene increased more than 30-fold. The following two types of mutations were found to be responsible for the multidrug resistant phenotype: (i) a nucleotide replacement in the region between the promoter and initiation codon of ImrA and (ii) nucleotide replacements that resulted in amino acid replacements in the LmrA protein. The results indicate that LmrB is a multidrug resistant protein and that LmrA is a repressor, which autogenously represses the transcription of the ImrAB operon.
Murata
Makiko
M
Department of Molecular Biology, School of Health Sciences, Kyorin University, Hachioji-shi, Tokyo 192-8508, Japan.
Ohno
Shinichi
S
Kumano
Miyuki
M
Yamane
Kunio
K
Ohki
Reiko
R
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000235:genetics; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial; D008034:Lincomycin / Q000378:metabolism / Q000494:pharmacology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009154:Mutation; D009693:Nucleic Acid Hybridization / Q000379:methods; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011691:Puromycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003062:Codon; D008034:Lincomycin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011691:Puromycin; C101824:LmrA protein, Lactococcus lactis