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 acts as an antimicrobial agent by interacting with endogenous reactive oxygen species such as hydrogen peroxide (H2O2) and superoxide (O2–) to generate reactive nitrogen species such as peroxynitrite (OONO–), S-nitrosothiols (RSNO), nitrogen dioxide (NO2), dinitrogen trioxide (N2O3), and dinitrogen tetroxide (N2O4). These reactive intermediates are able to target DNA, causing deamination, oxidative damage, strand breaks, and other DNA alterations.
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.