Combined effect of anti-mycobacterial plant extracts and their inhibitory effect on RNA polymerase and DNA gyrase gene of Mycobacterium tuberculosis

Abstract

Abstract Background Tuberculosis continues to be a serious health problem, and drug-resistant tuberculosis is an increasing threat that directly impacts the tuberculosis control program. These can be prevented or controlled by combining several drugs with antituberculous activity. In the present study, an attempt is made to understand the combinatorial effect of two medicinal plant extracts i.e. Piper longum and Cressa cretica against Mycobacterium tuberculosis.Methodology 2D checkerboard assay was used to study the combinatorial effect of the crude extracts. The 2-∆∆Ct method was used to determine the changes in gene expression of selected genes rpoB, gyrA and gyrB involved in transcription and DNA replication and intrinsic resistance of Mycobacterium tuberculosis to front-line drugs.Results Determination of the effect on gene expression at the subminimum inhibitory concentration of the crude extracts. The required MIC concentration, 125 µg/ml, was inversely reduced up to 7 µg/ml for P. longum. Similarly, the required MIC concentration of 250µg/mL of C. cretica is reduced to 10µg/mL.Conclusions The relative change in gene expression for rpoB and gyrA was 2 and 4-fold, respectively, and 1-fold for gyrB. Further characterization of the downstream target genes and in vivo studies may provide the mode of action of these two anti-mycobacterial agents.