Mechanisms and Action of Drug Resistance on <em>Mycobacterium tuberculosis</em>

Tuberculosis (TB) remains the most challenging infection to treat worldwide. The contemporary TB regimens consist of 6–9 months of daily doses of four drugs in the existing regimen that is extremely toxic to patients. The purpose of these longer treatments is to eliminate Mycobacterium tuberculosis, notorious for its ability to resist most antimycobacterial drugs, thereby preventing the formation of drug-resistant clinical strains. On the contrary, prolonged therapies have led to impoverished patient adherence. Furthermore, the severe limitations of drug choices have resulted in the emergence of drug-resistant strains. Unfortunately, the lack of great lethargy toward developing effective antituberculosis regimens with a large-scale prevalence rate is a tremendous challenge to controlling the pandemic. In fact, the current improvement in genomic studies for early diagnosis and understanding of drug resistance mechanisms, and the identification of newer drug targets, is remarkable and promising. Identifying genetic factors, chromosomal mutations, and associated pathways give new hope to current antituberculosis drug discovery. This focused review renders insights into understanding molecular mechanisms underlying the profound drug resistance. This knowledge is essential for developing effective, potent antibiotics against drug-resistant strains and helps shorten the current treatment courses required for drug-susceptible tuberculosis

Prevalence of mutations in genes associated with rifampicin and isoniazid resistance in Mycobacterium tuberculosis clinical isolates

Purpose: To analyze prevalence of mutations in genes associated with rifampicin and isoniazid resistance in Mycobacterium tuberculosis clinical isolates from patients with possible MDR TB of Puducherry, South India and to explore the association of specific mutations conferring rifampicin (RIF) resistance.Methods: We performed a commercial Genotype MDBDRplus V.2.0 assay for the rapid detection of rifampicin and isoniazid resistance directly on sputum specimens of patients with possible MDR TB.Results: Totally 558 multidrug resistant, 293 RIF mono resistant and 923 INH mono resistant tuberculosis were detected from the 12,786 patients with possible MDR TB samples. The 50.5% mutations were observed in the region of S531L in MDR TB patients and 55.6% in rifampicin monoresistant cases. In total isoniazid monoresistant, 68.0% mutations were detected in katG gene, which is more prevalent in comparison to inhA gene 32.0%. There were about 57.9% and 32.2% MDR TB cases diagnosed in the age group of >â15 to â¤â45 years and >â45 to â¤â60 years respectively.Conclusions: The rate of occurrences of mutations were found widely in the Rifampicin Resistant Determination Region (81bp) of rpoB gene and the hypervariable region 530â533 codons of rpoB gene is alarming in the specification. The higher frequency of mutation in codons of rpoB (S531L) and katG (S315T) gene help to design simple, new and less expensive molecular techniques to use in peripheral laboratories. Keywords: Mycobacterium tuberculosis, Multidrug resistant, Rifampicin monoresistant, Hypervariable region, Isoniazid monoresistan