Tuberculosis (TB), which is spread from person to person through the air, is one of
the top 10 causes of death worldwide with 1.8 million people dying from
the disease last year. Drug-resistant strains of TB have already been
identified in 105 countries.
Scientists have discovered a key 'survival gene' that prevents
strains of tuberculosis (TB) from mutating into drug-resistant
‘A gene called NucS dramatically reduces mutation rates in mycobacteria - the infectious microbe which causes tuberculosis. This discovery could prevent development of antibiotic resistance during treatments.’
In a joint study, published in the journal Nature Communications
scientists from the Centro Nacional de Biotecnología in Madrid and the
University of Sussex in Brighton, report the discovery of a gene called
NucS that dramatically reduces mutation rates in mycobacteria - the
infectious microbe which causes tuberculosis (TB).
The researchers involved in this study
believe that the identification of a key gene, required to suppress
mutation rates in mycobacteria, is an important step towards
understanding 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), the
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. More work needs to be done, but the scientists
believe this discovery could also play a role in understanding the
development of antibiotic-resistance in patients already suffering from
Professor Aidan Doherty, from the University of Sussex, said: "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. This knowledge will then enable us to better understand how
pathogens develop into 'superbugs'.
"Incredibly, for many years it was believed that mycobacteria lacked
any mutation avoidance genes. Therefore, 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. 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
Professor Jesus Blázquez, from the Centro Nacional de Biotecnología,
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."
"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