Antibiotics

Biography

Biography: Michael kelso

Abstract

Low concentrations of nitric oxide (NO) have been shown to act as a signal that induces biofilm bacteria to disperse and revert to the free-swimming (planktonic) form. This finding unveiled an exciting new anti-biofilm paradigm; i.e. use of NO-donor compounds in combination with antibiotics to clear chronic biofilm infections, sinceit is well-known that planktonic bacteria are up to 1000x more susceptible to antibiotics and host immune defences than their better-protected biofilm counterparts. Based on this discovery, we have designed, synthesized and provided in vitro proof-of-concept validation for a novel class of cephalosporin-based NO-donor prodrugs (DEA-CPs) that can provide biofilm-targeted NO delivery. The targeted NO signal from DEA-CPs (activated by ß -lactamases) induces biofilms to disperse and when used in combination with clinical antibiotics the compoundsare able to clear biofilms. The seminar will highlight key results in this area, including our latest efforts to translate DEA-CPs for use against chronic respiratory P. aeruginosa biofilms in cystic fibrosis patients.