Research Highlights

doi:10.1038/nindia.2015.151 Published online 17 November 2015

New defence against superbugs

Researchers have synthesized monomers and dimers of vancomycin aglycon that can inhibit the growth of various ‘superbugs’ ― bacteria that are resistant to multiple drugs1. These compounds killed bacteria more efficiently than existing antibiotics such as vancomycin and hence could emerge as powerful antibiotics.

Studies had shown that disease-causing bacteria such as Staphylococcus aureus and Enterococcus faecium have developed resistance to vancomycin, the most potent antibiotic.

To find effective antibiotics, the researchers synthesized vancomycin aglycon monomers and dimers containing positively charged fat-loving pockets that had an affinity for the negatively charged cell membranes of bacteria. They probed the antibacterial activities of the vancomycin derivatives by exposing them to vancomycin-sensitive and vancomycin-resistant S. aureus and E. faecium in culture and whole blood.

One of the vancomycin aglycon monomers showed a 115 times higher antibacterial activity against vancomycin-resistant E. faecium than vancomycin. The vancomycin aglycon dimers were also found to be more effective than vancomycin against vancomycin-resistant and vancomycin-intermediate-resistant S. aureus and vancomycin-sensitive E. faecium.

One of the dimers exhibited a 300 times higher antibacterial activity against vancomycin-resistant E. faecium than vancomycin. This dimer killed bacteria at low concentrations and retained its antibacterial activity in whole blood.

The vancomycin derivatives, particularly dimers, achieved such high antibacterial activities by efficiently inhibiting the biosynthesis of peptidoglycan, which helps build the bacterial cell wall, the researchers say.


References

1. Yarlagadda, V. et al. Lipophilic vancomycin aglycon dimer with high activity against vancomycin-resistant bacteria. Bioorg. Med. Chem. Lett. 25, 5477–5480 (2015)