A Comprehensive Review of Genetic Mechanisms of Mycobacterium tuberculosis Resistance to Injectable Agents, Second-Line Drugs, and Novel Therapeutics

Abstract: Tuberculosis (TB) has been one of the deadliest infectious diseases since ancient times and remains a major threat to public health, causing significant morbidity and mortality. The global TB outbreak in 1993 prompted the World Health Organization to declare the disease an emergency priority. However, public neglect and the ability of M. tuberculosis to develop drug resistance have led to the emergence of multidrug-resistant, extensively drug-resistant, and totally drug-resistant strains. These resistances are mainly caused by genetic mutations in antibiotic target genes, which reduce the effectiveness of drugs and make it more difficult to treat patients. In this review article, focusing on molecular and genetic mechanisms, the resistance of M. tuberculosis to injectable agents, second-line drugs, and novel anti-TB agents is investigated. Relevant studies were identified through a comprehensive search of major scientific databases, including PubMed, Scopus, and Web of Science. Articles were selected based on relevance to the molecular and genetic mechanisms of drug resistance in M. tuberculosis . The evidence was synthesized narratively to highlight current insights into resistance to anti-TB drugs. Keywords: M. tuberculosis , drug resistance, injectable agents, second-line drugs, novel agents, genetic mechanisms