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Antibiotic Adjuvants - Novel Molecules Restore b-lactam Potency Against Gram Negative Bacteria

Researchers at the University of Manitoba have developed novel aminoglycoside derivatives which defeat antimicrobial resistance mechanisms

Published: 9th June 2020
Antibiotic Adjuvants - Novel Molecules Restore b-lactam Potency Against Gram Negative Bacteria
University of Manitoba


Antimicrobial resistance is a global, serious threat to public health. Pathogenic Gram-negative bacilli, express multiple resistance mechanisms that work concertedly to shield them from the actions of antibiotics. It is estimated that by the year 2050, 10 million people annually will die of infections caused by drug-resistant pathogens.

The b lactam class of bacteria, from penicillin to the modern carbapenems are one of the most successful and versatile class of antibiotics. Resistant bacteria inactivate these drugs with b lactamases. The resistance mechanism is now being successfully fought with beta lactamase inhibitors in concert with beta lactam treatment. However bacteria are “learning” how to overcome the combination too.

Technology Overview

Multi-drug resistant gram negative bacteria cannot be treated with b-lactam antibiotics. Researchers have developed a novel aminoglycoside which derivatives defeat resistance mechanisms. These are intended as adjuvants to be co-administered with the antibiotics against gram-negative infections, including the ESKAPE group of carbapenem-resistant pathogens.

The researchers provides a group of adjuvant molecules. Their novel class is based on aminoglycoside molecules. These new drugs compromise the outer membrane, a powerful defence mechanism used by gram-negative bacteria. The molecules act by removing the energy source created by membrane porins and molecular efflux “pumps” in the membranes. The cyclam derivative is a novel way of overcoming the metalo-bLIs.


The compounds are effective in vitro at concentrations of 2 to 8 mM, and show low in vitro hemolytic activity and are well tolerated, over 100 uM in an insect in vivo toxicity model.


Treatment for Antimicrobial Resistance.


Available for license.

  • PCT/CA2019/050780
  • PCT/CA2016/050959 (search report available)
  • PCT/CA2020/0505656
IP Status
  • Provisional patent
  • Licensing
  • Development partner
  • Commercial partner