Effective Elimination of Drug Resistance Genes in Pathogenic Pseudomonas aeruginosa by Antipsychotic Agent Thioridazine

Pseudomonas aeruginosa is a serious threat in clinical medicine since most isolates are resistant simultaneously to many antibiotics at very high levels. Elimination of these resistances by known pharmacological compounds would be advantageous in successful therapeutic control of various infections caused by this bacterium. Levels of various antibiotics and thioridazine (Tz) resistances were determined in 12 P. aeruginosa strains including ATCC 27853 following standard procedure. Elimination or curing of antibiotic resistances was recorded in thioridazine treated strains. Agarose gel electrophoresis was carried out with DNA isolated from both wild type and cured strains following a standard protocol. All 12 strains were multiply resistant to many antibiotics including several β-lactams, cephalosporins, aminoglycosides, fluoroquinolones; however, piperacillin, carbenicillin, amikacin and ciprofloxacin were the only drugs whose resistance levels were much lower. Since, pseudomonas plasmids are fairly large in size, plasmid DNA isolation by normal alkaline lysis process was ineffective. Application of Qiagen kit for isolation of plasmids combined with a manual procedure successfully revealed presence of plasmid bands in wild type strains in the electrophoresis system. Such bands were absent in a few Tz treated cured clones. Pipercaillin and carbenicillin are still highly effective against P. aeruginosa, while the antipsychotic drug Tz is a potent agent able to eliminate drug resistance plasmids, which are much larger in size than the plasmids of other Gram negative bacteria. Since many antibiotics are administered together to patients suffering from infections caused by P. aeruginosa, simultaneous application of thioridazine to such patients may open up a new arena of therapy.