Harnessing the power of our immune system: antibiofilm effects of action of nitric oxide

Introduction: Hard-to-heal wounds pose a significant clinical challenge, resulting in poor patient quality of life and substantial economic burden. Polymicrobial communities within hard-to-heal wounds form complex biofilms that contribute to wound chronicity, delayed healing, and increased infection risk. Due to the tolerance of biofilms to the host immune response and wound treatments, such as antibiotic treatment and standard antimicrobial dressings, there is a clinical need for wound treatments able to effectively target biofilm in hard-to-heal wounds. Nitric oxide (NO) represents one such strategy, due to its ability to target specific mechanisms integral to biofilm survival. The aim of this study was to evaluate the evidence of exogenous NO as an antibiofilm agent.Methods:We conducted a narrative review of the evidence underlying the antibiofilm mechanisms of action of NO and discussed the ability of NO to serve as a single-agent antibiofilm therapeutic for the management of hard-to-heal wounds.Results:We identified and reviewed three key antibiofilm mechanisms of actions of NO. (1) The breakdown of biofilm extracellular polymeric substances (EPS), through the depolymerisation of polysaccharides, disruption to proteins, and cleavage of extracellular DNA, allowing further penetration of NO (or other exogenous antimicrobial or host defence molecules) to reach the microorganisms within. (2) The induction of biofilm dispersal, exposing the bacteria and making them more susceptible to antimicrobials. (3) The disruption of signal molecules preventing intra-biofilm bacterial communication (quorum sensing), resulting in reduced virulence of the biofilm bacteria and thus severity of infection.Discussion: The antibiofilm effects of NO suggest that the exploitation of NO generation from exogenous sources may represent a promising strategy for the management of biofilm in hard-to-heal wounds.References: