The effects of cannabispiro compounds and tetrahydrocannabidiolic acid on the plasmid transfer and maintenance in Escherichia coli.

Some cannabispiro compounds and tetrahydrocannabidiolic acid were tested for antibacterial plasmid curing activity and inhibition of plasmid transfer. MIC values of the compound were above 1500 micrograms/ml. Cannabispirol and tetrahydrocannabidiolic acid eliminated the F'lac plasmid from Escherichia coli, but acetylcannabispirol, cannabispirone and cannabispirenone were ineffective as curing agents. Each compound, except acetyl-cannabispirol, selectively killed plasmid carrying bacteria. The compounds inhibited R144 plasmid transfer from E. coli into E. coli cells via inhibition of mating pair formation, zygotic killing and inhibition of transconjugal DNA synthesis in a lesser extent. All of the cannabispiro compounds and tetrahydrocannabidiolic acid inhibited the transformation with pBR322 plasmid DNA when the bacteria were pretreated with the compounds, via inhibition of the DNA penetration or decreasing the synthesis of plasmid DNA during bacterial growth. Although each of the compounds, except acetyl-cannabispirol, had a weak antibacterial effect which was more definite on plasmid carrying bacteria than plasmidless ones, and inhibited intercellular plasmid transfer and transforming activity of plasmid DNA, only two of them were able to cure F'lac plasmid showing that plasmid elimination is a complex process which strictly depends on the stereochemical configuration of curing agents.