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. Due to the plurality of mechanisms responsible for bacterial inactivation, there is a low tendency for the bacteria to develop antimicrobial resistance. Additionally, NO is also effective against both planktonic bacteria and biofilms, the latter of which are notoriously difficult to treat due to the presence of an exopolysaccharide matrix that is resistant to penetration by antibiotics.
This is a major research stream in our laboratory and we have developed nitric oxide releasing platforms (nanoparticles, gels, 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 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). The covalent immobilization or encapsulation of these AMPs has the potential to improve efficacy and localized availability. We are developing nanodelivery vehicles of these AMPs for the treatment of surgical site 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.