London: Scientists have discovered a key “survival gene” that prevents strains of tuberculosis (TB) from mutating into drug-resistant ‘superbugs’.
Researchers from the Centro Nacional de Biotecnologia in Spain and the University of Sussex in the UK identified the gene called NucS that dramatically reduces mutation rates in mycobacteria — the infectious microbe which causes TB.
TB, which is spread through the air, is one of the top 10 causes of death worldwide, researchers said.
Drug-resistant strains of TB have already been identified in 105 countries and researchers believe that a key gene, required to suppress mutation rates in mycobacteria, may help understand how “superbugs” develop.
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), scientists discovered that a DNA repair enzyme, produced by the NucS gene, dramatically reduces mutations from occurring.
The researchers also discovered that genetic variations in the NucS gene significantly influence the mutation rates in clinically isolated strains of mycobacteria.
The scientists believe the discovery could also play a role in understanding the development of antibiotic-resistance in patients already suffering from TB.
“The rise of antibiotic resistance is a major threat to global health and, if we are to limit its impact on infectious diseases, we first need to identify the mechanisms that prevent bacteria from mutating in the first place,” said Aidan Doherty, a professor at the University of Sussex.
“This knowledge will then enable us to better understand how pathogens develop into ‘superbugs’”, Doherty said.
“Incredibly, for many years it was believed that mycobacteria lacked any mutation avoidance genes,” he said.
The discovery that the NucS gene reduces the rate at which mutations occur in these pathogens is a crucial first step towards identifying the genetic factors that influence the onset of antibiotic-resistance,” said Doherty.
“This will enable scientists and clinicians to screen for strains that are most likely to develop drug-resistance and figure out strategies to tackle this serious threat,” he said.
“Not only does this study identify that mutations can be reversed in mycobacteria, it reveals that the loss of this DNA repair process can cause a huge increase in the mutation rates, significantly increasing the likelihood of these pathogens acquiring mutations — which can cause antibiotic resistance,” Professor Jesus Blazquez, from the Centro Nacional de Biotecnologia, said.
“Now we know that that NucS dramatically reduces mutation rates in mycobacteria — it is vital that we take advantage of this and work towards exploiting this discovery to help doctors and microbiologists to predict and prevent the development of antibiotic resistance during treatments,” said Blazquez.
The study was published in the journal Nature Communications.
