Abstract
Tuberculosis (TB) is among the most common infectious diseases and frequent causes of death worldwide claiming many of lives annually. The problem of tuberculosis is hampered by the emergence of multi drug resistant(MDR) and extensively drug resistant (XDR) tuberculosis. Anti-tuberculosis drugs are a two-edged sword. While they destroy pathogenic Mycobacterium tuberculosis they also select for drug resistant bacteria against which those drugs are then ineffective. In contrast to other bacteria, resistance of M. tuberculosis is exclusively associated with chromosomal mutations. Globally, the emergence of multidrug-resistant strains of M. tuberculosis is an increasing problem which adversely affects patient care and public health. The objective of this review is therefore to compile available literatures about the drug resistance mechanisms of M. tuberculosis which gives insight understanding for the development of new therapeutic and diagnostic methods for the management of MDR and XDR tuberculosis infections. Resistance to first line anti-TB drugs has been linked to mutations in at least 10 genes; katG, inhA, ahpC, kasA and ndh for INH resistance; rpoB for RIF resistance, embB for EMB resistance, pncA for PZA resistance and rpsL and rrs for STR resistance. The search for new anti-tuberculosis drugs shall consider new targets which are less susceptible for mutation.
Highlights
Tuberculosis (TB) is among the most common infectious diseases and frequent causes of death worldwide [1]
An estimated one third of the world’s population is infected with Mycobacterium tuberculosis, and nearly 9 million persons develop disease caused by M. tuberculosis each year [2]
RIF resistance is associated with a hotspot core region called rifampicin resistance determining region ( RRDR), for “rifampicine resistance determining region” (81 bp) of the rpoB gene with more than 95% of RIF resistant M. tuberculosis has a mutation in this specific zone [20]
Summary
Tuberculosis (TB) is among the most common infectious diseases and frequent causes of death worldwide [1]. An estimated one third of the world’s population is infected with Mycobacterium tuberculosis, and nearly 9 million persons develop disease caused by M. tuberculosis each year [2]. In 2009, there were an estimated 14 million prevalent and 9.4 million incident cases. Among 5.8 million notified cases of TB patients in 2009, an estimated 250 000 had multidrug resistant TB (MDR-TB) [3]. Ethiopia ranks seventh among the world’s 22 highburden tuberculosis (TB) countries. According to the World Health Organization’s (WHO’s) Global TB Report 2009, the country had an estimated 314,267 TB cases in 2007, with an estimated incidence rate of 378 cases per 100,000 population [4]
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