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‘Survival gene’ stops strains of TB mutating into deadly ‘superbugs’

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'Survival gene' stops strains of TB mutating into deadly 'superbugs'

Multi-collaborative research has identified a key ‘survival gene’ that prevents strains of tuberculosis (TB) from mutating into drug-resistant ‘superbugs’.

Published in the journal Nature Communications, the study reported the discovery of a gene called NucS that dramatically reduces mutation rates in mycobacteria – the infectious microbe that causes TB.

Tuberculosis is the leading cause of death worldwide by an infectious disease, killing 1.8 million people every year. Drug-resistant TB is on the rise, with drug-resistant strains of the disease identified in 105 countries and TB accounting for one-third of all drug-resistant bacterial infections. The research team believe that the identification of this key pathway, required to supress mutation rates in mycobacteria, is an important step towards understanding how ‘superbugs’ develop.

Dr Simon Waddell from BSMS and the Wellcome Trust Brighton and Sussex Centre for Global Health Research collaborated on the research with Professor Aidan Doherty (Genome Damage and Stability Centre, University of Sussex), Professor Jesus Blázquez (Centro Nacional de Biotecnología, Spain) and Dr Mark Paget (Biochemistry, University of Sussex). 

“Discovery of the NucS pathway controlling mutation rates in mycobacteria is an exciting step towards tackling tuberculosis,” said Dr Waddell. “This pathway may influence the emergence of drug-resistant TB in patients during treatment, allowing us to screen for TB strains that are likely to develop drug resistance. Insights into the basic biology of TB bacteria will help us to develop new strategies against the disease and enable drugs to be used more effectively in the clinic.”

Using a genetic screen, which involved individually knocking out nearly every gene (11,000 genes) in mycobacteria, and screening whether mutant strains grew on a specific antibiotic (rifampicin), the scientists discovered that a DNA repair enzyme, produced by the NucS gene, dramatically reduces mutations from occurring. They also discovered that genetic variations in the NucS gene significantly influence the mutation rates in clinically isolated strains of mycobacteria, which could lead to a greater understanding of the development of antibiotic resistance in patients already suffering from TB.

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