Some bacterial plasmids undergo spontaneous loss at low frequency. Plasmids can be eliminated by the use of tricyclic drugs to increase the so frequency of segregation. The purpose of this study is to clarify the specific mechanism of action of the called antiplasmid drugs on various plasmids. The antibiotic resistance coding plasmids were eliminated from E. coli, Proteus vulgaris, P. mirabilis, Acinetobacter anitratus, K. pneumoniae, Agrobacter tumefaciens and Staphylococcus aureus strains with a frequency of from 0.2 to 15% by promethazine and amitriptiline. The colicin V production of E. coli strains, the pigment production of S. marcescens and S. aureus, the haemolytic activity of some S. aureus and E. coli cells, the nod plasmid of R. meliloti and the virulence plasmids of A. tumefaciensis and Y. enterocolitica were eliminated in the presence of plomethazine. The antiplasmid compounds affect the topological state of plasmid DNA. The superhelical form of DNA is diminished and the linear form increased in the presence of antiplasmid compounds. The biological activity of plasmid DNA in transformation is also decreased. The binding affinity of antiplasmid H3 imipramine is ten times higher for the supercoiled form of plasmid DNA than for the linear form. Transconjugal plasmid transfer is inhibited as well. The process in this way results in plasmid-free bacteria in the population. Quantitative structure-activity relationship studies (QSAR) revealed some correlations between the antiplasmid effect the symmetry of the HOMO orbitals and the electrophilic superdelocalizibility on atoms C8, C9 and N10 of the tricyclic skeleton. Antiplasmid compounds form charge-transfer complexes with plasmid replication machinery. The elimination of plasmids conferring pathogenicity and resistance to antibiotics can open up new horizons is experimental chemotherapy.
|Number of pages||7|
|Publication status||Published - Dec 1 1994|
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