Salicylanilide Derivatives Potentiate Colistin Activity
Tech ID: 20-016
Inventor: Dr. Christian Melander
Date added: July 30, 2020
Novel small molecules that reverse bacterial resistance to the antibiotic colistin.
Infections caused by multi-drug resistant (MDR) bacteria, particularly Gram-negative bacteria, are responsible for around 33,000 deaths in the US each year. Clinicians are often forced to administer the last resort antibiotic colistin to combat bacterial infections, however colistin resistance is becoming increasingly prevalent, giving rise to the potential for a situation in which there are no treatment options for MDR Gram-negative infections. The development of adjuvants that circumvent bacterial resistance mechanisms is a promising approach to the development of new antibiotics, as there are currently no approved molecules that reverse colistin resistance. Adjuvants typically posses little stand-alone microbicidal activity, but instead target antibiotic resistance mechanisms. When paired with the appropriate antibiotic, these antibiotic/adjuvant combinations provide a powerful treatment for MDR bacteria.
Researchers at the University of Notre Dame have recently discovered novel salicylanilide derivatives that reverse colistin resistance in Gram-negative bacteria via adjuvant activity. Introduction of this molecule with colistin as an adjuvant/antibiotic treatment for bacterial infections could help reverse the antibiotic resistance problem and expand colistin’s therapeutic use beyond a last-resort treatment option and at lower doses.
• Reverses antibiotic resistance of A. baumannii, K. pneumoniae, and E. coli to colistin, expanding the limited viable treatment options for bacterial infections.
• Reduces the minimum inhibitory concentration (MIC) of colistin upwards of 4096-fold.
Structure-Function Studies on IMD-0354 Identifies Highly Active Colistin Adjuvants.
Technology Readiness Status
TRL 3 - Experimental Proof of Concept