Investigation of drugs that inhibit Escherichia coli and mycobacterial growth

Tuberculosis (TB) remains a deadly disease to this day, despite antibiotic treatments being available to effectively cure this disease. One of the main reasons for therapeutic failure is because the organism responsible for the disease, Mycobacterium tuberculosis, is becoming resistant to many life-saving drugs like rifampicin. Thus, the search for substitutes to treat TB is ongoing, with phenothiazines being prime candidates. These drugs – primarily used to combat mental illnesses like schizophrenia – have shown excellent antitubercular properties in the past, but conventional TB drugs quickly took their place, owing to long-term toxicity of phenothiazines. However, in the battle against multidrug resistant TB, one particular phenothiazine, thioridazine, has gained some attention on account of its milder side effects. While it successfully inhibits mycobacteria, Escherichia coli are unaffected. This study focused on the multifunctional gene mreB, present in E. coli but absent in mycobacteria, hypothesizing that mreB confers a protective effect against thioridazine. To test this hypothesis, E. coli mutants lacking mreB, and Mycobacterium smegmatis were grown in the presence of thioridazine and subsequently transformed with a plasmid carrying the mreB gene. Finally, bacteria were grown in the presence of thioridazine to compare their growth before and after plasmid transformation. Whereas transformed E. coli mutants exhibited restored growth in the presence of thioridazine, M. smegmatis did not. While these findings underscore the potential role of mreB in mediating drug resistance, further research with different plasmids and similar genes will give more insight into the inhibitory mechanism of phenothiazines against mycobacteria.