Thiolutin resistant mutants of Escherichia coli are they RNA chain initiation mutants?

Abstract

Four mutants of Escherichia coli KL16 resistant to the antibiotic Thiolutin have been isolated. This drug was earlier reported to be an inhibitor of RNA chain elongation. The first mutant, TL^rI, is resistant only in rich or partially rich media: it can, however, grow in minimal medium containing the drug with a very long doubling time. The other mutants TL^rII, TL^rIIIa and TL^rIIIb are resistant in rich as well as minimal media.β -galactosidase could not be induced in TL^rI and TL^rII in the presence of thiolutin whereas the enzyme is constitutively synthesised in TL^rIIIa and TL^rIIIb irrespective of the drug. The mutants do not support the development of phage T4 in presence of the drug, if the drug is added along with the phage, but escape the inhibition if phage development is allowed to proceed for some time before the addition of the drug. The time of this escape is characteristic of the mutant. Even in a sensitive strain, T7 growth escapes inhibition very soon after infection, around the time the phage-specific RNA polymerase is synthesised. In the parent strain the kinetics of inhibition of β -galactosidase induction resembles more the inhibition caused by rifampicin than by streptolydigin. It is proposed that thiolutin could be an inhibitor of RNA chain initiation and resistance might be due to mutation in the subunit(s)/factor(s) involved in initiation.