Nitric oxide, Antimicrobial peptides, Metals
Nitric oxide (NO) is a potent broad spectrum antimicrobial and part of the body’s defense mechanism that is activated by inflammatory cells (neutrophils and macrophages) which are responding to invading pathogens such as bacteria, protozoa, and fungi. NO can kill bacteria with several different mechanisms, which means that it is very difficult for bacteria to develop resistance. NO has also been shown to have activity against both planktonic (free floating) bacteria and biofilms (adhered bacteria), the latter of which are notoriously difficult to treat due to the presence of an exopolysaccharide matrix that is resistant to penetration.
This is a major research stream in our laboratory and we have developed nitric oxide releasing platforms (nanoparticles, gels, nanofibers, surfaces) for treating infections in the eye, skin and bone.
Antimicrobial Peptides (AMPs) are produced by all complex organisms as well as some microbes as part of innate immune response, and display diverse and complex antimicrobial activities against a broad range of Gram negative and Gram positive bacteria( including those that are resistant to established antibiotic drug therapies), mycobacteria, enveloped viruses, parasites and fungi. They have gained increasing popularity as a possible alternative to antibiotics due to their broad spectrum activity, low toxicity and most importantly their low tendency to induce antimicrobial resistance (AMR). We have developed antimicrobial surfaces which have been tethered with AMPs and AMP-loaded nanogels and 3D printed devices for the treatment of antibiotic resistant infections.
Metals have served as antimicrobial agents for a very long time, yet for most of history, their mechanisms of action have been shrouded in mystery. Recent research suggests that various metals inflict specific and separate forms of harm on microbial cells, such as oxidative stress, protein malfunction, or damage to the cell membrane. We have developed silver and copper doped materials that have shown excellent efficacy for the treatment of drug resistant infections.