Çoklu ilaç dirençli mycobacterium tuberculosis'de yüksek ve düşük isoniazid direncinin moleküler genetik farklılıkları

Tuberculosis is one of the top ten causes of death worldwide. Isoniazid (INH) is an one of the important major chemotherapeutic and prophylactic drug against TB and it is key component of global tuberculosis (TB) control programs which we cannot afford to lose. INH prophylaxis reduces the risk of developing TB (suspicious and latent). Also it is cheap, effective and has a low rate of adverse events that cannot be substituted by an equally positive alternative. INH resistance to is typically caused by mutations katG and inhA promoter regions. katG mutations confer high-level isoniazid resistance while inhA mutations confer low-level resistance to isoniazid. In this study, we investigated which genetic mutations predict the level of phenotypic isoniazid resistance. For this purpose, phenotypic resistance of 91 INH resistant isolates was determined at 3 different drug levels and four gene regions associated with INH drug resistance, including KatG, furAlG, fabGl-pro inhA and inhA, were amplified and sequenced. As a result of this study, we found Mutations in the promoter region of inhA tend to result in low-level, katG Ser315Thr mutations moderate and the combination of katG Ser315Thr and inhA c-15t tend to high level phenotypic resistance. No clear association was found between mutations other than these and isoniazid the level resistance.