The photographs show MRSA growing on the surfaces of two agar plates, one without guanosine (left) and one with guanosine (right) onto which disks soaked with antibiotics have been applied. The zones of clearing around the antibiotic disks are indicative of MRSA killing. Credit: University of Galway
Key points:
- Scientists have discovered a new way to improve treatment options for MRSA.
- Experiments showed adding purines, the building blocks for DNA, to common antibiotics “re-sensitizes” the superbug.
- The findings have implications beyond just antibiotic resistance, including for cancer treatments.
Antibiotic resistance is one of the greatest threats to human health, with superbugs like MRSA placing a significant burden on global healthcare resources.
Now, scientists at the University of Galway have shown that MRSA could be much more efficiently killed by penicillin-type antibiotics when combined with purines, which are the building blocks for DNA.
“This discovery is important because it has revealed a potentially new way to treat MRSA infections with penicillin-type drugs, which remain the safest and most effective antibiotics,” said study author James O’Gara, professor of microbiology.
Purine nucleosides, adenosine, xanthosine, guanosine are sugar versions of the building blocks of DNA, and the researchers say their work shows that they interfere with signaling systems in the bacterial cell.
“It appears that under β-lactam stress, MRSA may attempt to limit flux through purine biosynthetic pathways as a means of increasing resistance and that, conversely, increased guanosine or xanthosine flux into the GTP branch of purine metabolism has the reverse effect and reduces β-lactam resistance,” say the researchers.
The work, published in mBio, focuses on using purines to “re-sensitize” MRSA to oxacillin and other β-lactam antibiotics—which are generally considered the safest class of antibiotics.
“Mechanistically, exposure of MRSA to these nucleosides significantly reduced the levels of the cyclic dinucleotide c-di-AMP, which is required for β-lactam resistance,” the team wrote in the paper.
In addition to antibiotic resistance, drugs derived from nucleotides are also widely used in the treatment of cancer and viral infections, further highlighting the clinical potential of using purine nucleosides to restore or enhance the therapeutic effectiveness of β-lactams.
“Using purine nucleosides as adjuvants to increase the susceptibility of clinically important pathogens to β-lactams has the potential to facilitate new treatments with lower antibiotic doses and with drug combinations that are toxic at higher concentrations,” the team concluded.