Pathogenesis, Treatment and Molecular Mechanisms for Development of Multidrug-resistant (MDR) TB as well as Identification of MDR Mycobacterium Tuberculosis
Nøgleord:
molecular mechanisms, molecular methods, multidrug resistance, mycobacterium tuberculosis, tuberculosisResumé
Tuberculosis (TB) is a medical, social, and economic disaster of huge magnitude in the world. Prevalence of TB has increased due to poverty, population growth, migration and a high number of TB cases in HIV positive individuals. High prevalence rate of M. tuberculosis strains with multidrug resistance (MDR) is a serious problem as global emergency. Strains of M. tuberculosis resistant to both rifampicin and isoniazids with or without resistance to other drugs have been termed as multi-drug resistant. Causes of MDR are genetic factors and factors associated to previous anti tuberculosis treatment. MDR resistance is acquired by the bacilli either by alteration of the drug target through mutation or by titration of the drug through overproduction of the target. Molecular methods use variety of methods with multiple protocols of nucleic acid extraction and amplification (PCR) of different genetic targets; IS6110, rpoB, hsp65, 16S rDNA or MBP64. Of different techniques, electrophoresis, sequencing and hybridization assays are widely used. Sequencing based assays directly determine mutations and can specifically and precisely show mutations involved; while electrophoretic assays roughly provide an indirect method for the determination of mutations without showing the exact nucleotidic substitution. Molecular methods such as polymerase chain reaction (PCR) based sequencing, PCR–SSCP (single-strand-conformation polymorphisms), PCR–DNA sequencing, real-time PCR, multiplex allele-specific PCR, micro array technology, restriction fragment length polymorphism, solid phase hybridization assay, INNO-LiPA Rif, GenoType MTBDR, GenoType MTBDRplus, mycobacteria growth indicator tube and Ligase chain reaction are currently used. Solid-phase hybridization assays and RTPCR have been commercialized. New researches for mechanisms of MDR-mycobacterium TB and for development of new diagnostic tools and effective drugs are needed. Fast and rapid diagnosis of tuberculosis (TB) and multidrug-resistant in M. tuberculosis is one of the vital needs for global TB control as it allows early epidemiological and therapeutic prevention.Downloads
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