New research has highlighted a gene, NucS, which can prevent tuberculosis-causing bacteria from mutating into antibiotic resistant strains.
The work was carried out by scientists from the University of Sussex, UK, and the Centro Nacional de Biotechnologia, Madrid, and was published on the 27th January 2017 in Nature Communications.
NucS is a gene which is responsible for producing a DNA repair enzyme. DNA repair is essential for limiting the amount of errors which can appear in an organism’s genome, thereby protecting that organism from undergoing a potentially harmful mutation. There are several repair mechanisms such as mismatch repair (MMR), a pathway which is similar across all forms of life, from mammals to bacteria. However, until this study, scientists were uncertain as to what exactly the key players protecting mycobacteria from mutation were.
NucS was initially uncovered when the research team carried out a genetic screen on Mycobacterium smegmatis. They individually ‘switched off’ almost each gene of the bacteria’s genome, one by one, and watched to see how the mutation rate of the bacteria was affected by growing them on rifampicin, an antibiotic used in the treatment of TB. When NucS was silenced, they found that spontaneous mutation rates shot up.
When the team generated strains of M. smegmatis with the NucS gene deleted and tried to grow it on antibiotics, they found that resistance to rifampicin shot up by 150-fold, while resistance to streptomycin increased 86-fold.
TB is one of the most serious diseases facing us, transmitted through the air and posing a particular threat to young children and those with an immune-deficiency. Last year, approximately 1.8 million deaths were attributed to the disease. Multidrug resistant TB is also a huge problem, especially in China, India and the Russian Federation.
The new information that this study has provided puts us one step closer to understanding, in greater detail, how resistance in TB can occur. Professor Jesus Blázquez, one of the researchers from the Centro Nacional de Biotechnologia, said of the study: “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 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.”
According to the website of the University of Sussex, a follow up study has been funded by the Biotechnology and Biological Sciences Research Council. The University will again work with the research team in Madrid to further the understanding of how NucS acts to prevent mutations in mycobacteria.