Scientists in Japan have revealed how vancomycin dimers are effective against vancomycin-resistant bacteria.

Vancomycin, a glycopeptide antibiotic, is used to treat bacterial infections in cases when other antibiotics are ineffective. However, the development of vancomycin resistant enterococci (VRE) and Staphylococcus aureus means that researchers are turning to different forms of vancomycin to improve its efficacy.

Hirokazu Arimoto at Tohoku University, Sendai, and colleagues had previously shown that  vancomycin dimers displayed excellent antibacterial activity against vancomycin-resistant bacteria. Now, they have shown how the dimers interact with the bacteria.

’Vancomycin-resistance is a serious concern because vancomycin is the last resort drug in the treatment of bacterial infections [such as methicillin-resistant Staphylococcus aureus (MRSA)],’ explains Arimoto.

Vancomycin works by inhibiting the synthesis of the bacteria’s cell walls so the team investigated how the dimer form affected cell wall synthesis in vitro. They found that both inhibited the synthesis, but their modes of action were different. Vancomycin inhibits the synthesis of peptidoglycan - a polymer that forms the cell wall - by attaching to its precursor molecule, whereas the dimer inhibits the polymerisation step in the peptidoglycan synthesis. 

’The inhibitory effect of these dimers on bacterial cell wall synthesis hadn’t been addressed,’ comments Jieping Zhu, an expert on the medicinal chemistry of vancomycin at the Federal Polytechnic School of Lausanne, Switzerland. ’So the finding that vancomycin dimers exhibit antibacterial activity against VRE through the suppression of cell wall synthesis is truly remarkable and marks an important step for understanding the precise mode of action of these compounds,’ he says. 

In the future, Arimoto and coworkers aim to carry out further assays using purified bacterial enzymes to confirm that the vancomycin dimers are targeting the cell wall polymerisation step. 

Leanne Marle 

Link to journal article

New insight into the mode of action of vancomycin dimers in bacterial cell wall synthesisOsamu Yoshida, Jun Nakamura, Hidenori Yamashiro, Kenji Miura, Sayaka Hayashi, Kosei Umetsu, Shu Xu, Hideki Maki and Hirokazu Arimoto,?Med. Chem. Commun., 2011, 2, 278DOI:10.1039/c0md00230e