Harnessing the power of our immune system: the antimicrobial mode of action of nitric oxide

Introduction: The presence of microorganisms, development of biofilm, and local infection play a significant role in the pathogenesis of hard-to-heal wounds. Systemic antimicrobial therapy plays a crucial role in managing infected hard-to-heal wounds, while antimicrobial dressings are used to manage wound bioburden. However, the increasing prevalence of antibiotic resistance, and the emerging appreciation of biofilm tolerance to standard antiseptics, presents a challenge to effective treatment. Nitric oxide (NO) is an integral and highly conserved factor of the host immune response, to which the risk of development of bacterial resistance is significantly diminished. The aim of this study was to evaluate the evidence of exogenous NO as an antimicrobial agent and assess the potential use of NO generation in wound dressings for the management of hard-to-heal wounds.Methods:We conducted a narrative review of the evidence underlying the antimicrobial mechanisms of action of NO and discussed the ability of NO to serve as an antimicrobial agent in the treatment of hard-to-heal wounds.Results:We identified and reviewed three key antimicrobial targets of NO. (1) Cell wall activity: NO freely penetrates and damages bacterial cell walls, NO inactivates extracellular cell wall proteins preventing bacterial transport systems and communication, and NO inactivates internal cell wall proteins, all which can result in cell death. (2) DNA activity: NO destroys microbial DNA, resulting in cell dysfunction and microbial cell death, and NO inhibits DNA replication causing bacteria to become unstable, unable to reproduce, and ultimately die. (3) Enzyme activity: NO inactivates iron-sulphur clusters, essential co-factors in enzymes involved in metabolic processes, resulting in bacterial cell death.Discussion: The exploitation of NO generation from exogenous sources represents a promising strategy as an antimicrobial agent, which has the potential to be used in wound dressings, for the treatment of hard-to-heal wounds.References: