Antiplasmid activity: loss of bacterial resistance to antibiotics.

The antiplasmid activity of tricyclic compounds, e.g. phenothiazines, dibenzoazepines, dibenzocykloheptene derivatives and some stereoisomers, was shown on E. coli in vitro. Some ring-substituted phenothiazine and cannabis derivatives had only an antibacterial effect. Promethazine, a selected phenothiazine, cured antibiotic resistance and lactose fermentation of E.coli, tumour inducing ability of Agrobacterium tumefaciens and nodule formation of Rhizobium meliloti. Plasmids of different E.coli strains were eliminated with varying frequency. The antiplasmid activity of the compounds can be due to the increased membrane permeability. Inhibition of DNA gyrase and complex formation with the supercoiled form of plasmid DNA can lead to the cessation of plasmid replication in the bacterial cells. In addition, in vivo plasmid curing was demonstrated at a low frequency.