Mutations in tuberculosis bacteria cause resistant to drugs

Mutations in tuberculosis bacteria cause resistant to drugs
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Tuberculosis is a deadly disease and can play havoc with one’s life. Research has been on the ascertaining the drug composition meant to treat.
The bacteria that cause tuberculosis (TB) have rather mutated and may soon become resistant even to the most recent drugs, such as Bedaquiline. What is worse, the diagnostic kits made use of in India for drug-resistant TB cannot indeed spot them either.

The scientists have rather discovered several mutations in the genes of TB bacteria thus causing drug resistance. The results of the four-year research were rather published in the latest issue of Frontiers in Microbiology, a scientific journal.

The team comprising researchers from the Institute of Bioinformatics, Bengaluru; Indian Council of Medical Research (ICMR), National Jalma Institute of Leprosy and other Mycobacterial Diseases, Agra; and Yenepoya University, Mangaluru. It has indeed been funded by the Department of Biotechnology (DBT), Infosys Foundation and Yenepoya University.

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Whole-genome sequencing:

The researchers who performed whole-genome sequencing of mycobacterium tuberculosis (MTB) strains did collect between 2010 and 2014 at the National Jalma Institute of Leprosy and Other Mycobacterial Diseases at Agra. The focus being on mutations in tuberculosis make it resistant to drugs
The analysis was carried out on 200 MTB strains from different categories such as sensitive to first-line drugs, rifampicin mono-resistant, isoniazid mono-resistant, streptomycin mono-resistant, MDR (multi-drug resistant) and pre-extensively drug-resistant (pre-XDR).

Genetic variations:

The research team also did identify several novel genetic variations and novel genotypes in clinical strains from north India, which might of course potentially be associated with drug resistance.
Nearly 20% of the strains were also co-infected with non-tuberculous mycobacteria species along with MTB. Efforts were on to identify a total of over 12,000 novel genetic variations in MTB isolates (strains), including 343 novel single nucleotide variations (SNVs) in 38 genes, which are indeed actually known to be associated with drug resistance. A large majority of these SNVs are not indeed currently, in fact, made use of in the diagnostic protocols for detection of drug-resistant TB. The results have been indeed quite surprising. Suspicion has been there about co-infections and one’s tools are all that adequate to detect organisms and drug-resistance accurately. Mutations in tuberculosis make it resistant to drugs is an acknowledged fact.

Anti-Tuberculosis drugs:

For TB treatment, the first-line of anti-tuberculosis drugs made use of are isoniazid, rifampicin, ethambutol, and pyrazinamide. The second-line anti-tuberculosis drugs are moxifloxacin, high dose levofloxacin (fluoroquinolones) and linezolid, demand, and bedaquiline.
Of these, bedaquiline happens to be the latest drug with increasing evidence of success against MTB. The Rv0678 gene in the TB thus causing bacteria which is known to be associated with bedaquiline resistance. Bedaquiline is indeed commonly made use of by the Union health ministry for treating TB. The researchers also indeed found a genetic variation in the Rv0678 gene in some of the MTB isolates sequenced. Mutations in tuberculosis make it resistant to drugs it has also been observed.

Thus keeping in mind that bedaquiline is a fairly new anti-TB drug, the identification of SNVs in this gene does suggest that the dynamic and rapid evolution of MTB clinical strains

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About the Author: Nagendra Gadamsetty

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