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Increasing the Efficacy of Vancomycin: Natural Compounds to Reduce Resistance

Technology Overview

Scientists at Leiden University's Institute of Biology have found a compound that decreases the resistance of vancomycin-resistant bacteria.

The sensitizing effect of this compound increases further when the activity of other vancomycin-resistance enzymes are targeted. Their work offers new perspectives for the treatment of diseases associated with vancomycin-resistant pathogens and for the development of drugs that target vancomycin resistance.

Vancomycin is nowadays primarily used to treat serious infections caused by gram-positive bacteria that are known or suspected to be resistant to other antibiotics. Acquired resistance to vancomycin by gram-positive bacteria, mediated through a plasmid-transmittable vancomycin resistance cluster, is a growing problem in the nosocomial environment. Vancomycin resistance evolved in common pathogenic organisms during the 1990s and 2000s, including vancomycin-resistant Staphylococcus aureus (Figure 1).

Vancomycin is a well-known drug against infections with Gram-positive pathogens, the World Health Organization's List of Essential Medicines, a basic health system.

Vancomycin targets the cell wall by specifically binding to the termini of the peptidoglycan precursor lipid II, prior to its incorporation into mature. The resulting weakening of the cell-wall integrity then leads to osmolysis. The termini are universally conserved in bacteria. The Leiden scientists have found the addition of a natural compound to the vancomycin-resistant model organism Streptomyces coelicolor, as well as clinical isolates of Enterococcus faecium dramatically enhanced the efficacy of vancomycin. Fluorescence imaging or S. coelicolor mycelia using BODIPY vancomycin showed that the enhanced vancomycin sensitivity correlated directly to increased binding of the antibiotic to the cell wall.

FIG. 1. Reduction of vancomycin tolerance or S. coelicolor M145 (a naturally vancomycin-resistant  model organism)

Details and State of Development:

Proof-of-concept, with further development:

- Study the activity of homologues of the identified inhibitor.
- Screen of novel compounds as inhibitors
- Structural analysis of the interaction between vancomycin resistance enzymes and their inhibitors
- Test efficacy against clinically relevant vancomycin-resistant Enterococci


Antibiotic adjuvant strategies: use of (natural) compounds that reduce resistance to vancomycin.


Currently, the scientists are seeking partnerships for the next stage of development.

Keywords: antibiotics, antibiotic resistance, antibiotic adjuvant, vancomycin


Key benefits

  • The compound that reduces vancomycin resistance is a natural product
  • The scientists propose a new model for vancomycin resistance which may allow identification of analogues/novel compounds

Luris reference number


Patent status

A priority patent application has been filed

Data available on request

Non-confidential and confidential presentations are available upon request

Further information

Frits Fallaux Coordinator / Sr. Business Developer +31-71-527 2517