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Michael kelso

Michael kelso

University of Wollongong, Australia

Title: Biofilm Dispersing NO-Donor Cephalosporins Activated by b-Lactamase

Biography

Kelso graduated from the University of Wollongong with a B. Medicinal Chemistry (1996) and received his PhD (Peptidomimetics, 2002) from the University of Queensland (Australia). After a 1-year postdoc with Prof Claudio Palomo (Universidad del Pais Vasco, Spain) studying catalytic asymmetric synthesis he moved to The Scripps Research Institute (CA, USA), where he studied medicinal chemistry as an NHMRC CJ Martin Fellow under Professor Dale Boger. Upon returning to Australia in 2006 he completed his Fellowship under Prof John Bremner at the University of Wollongong, where he was subsequently appointed as a lecturer (2008) and promoted to A/Prof (2014). His research group focuses on the design, synthesis and biological evaluation of antibacterials acting via novel mechanisms

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.

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