(PI-027) Complementing Our Immune System: The Antimicrobial Mode of Action of Endogenous Nitric Oxide and Its Potential in Wound Care

Scarlet Milo, PhD – R&D Program Advisor, Advanced Wound Care R&D, Convatec Ltd; Jonathan Roberts, PhD – R&D Scientist, Advanced Wound Care R&D, Convatec Ltd

Introduction: Hard-to-heal wounds, such as diabetic foot ulcers, are highly prevalent and place a significant burden on patients and healthcare systems. The aim of this review was to evaluate nitric oxide (NO) as an antimicrobial agent and assess the potential of NO-generating wound dressing technology* for the management of hard-to-heal wounds. The presence of microorganisms plays a significant role in the pathogenesis of hard-to-heal wounds. Systemic antimicrobial therapy has a crucial role in treatment of infected hard-to-heal wounds, while antimicrobial dressings are used to manage wound bioburden. However, there is emerging recognition of biofilm tolerance to standard antimicrobials, which, coupled with the prevalence of antibiotic resistance, presents a challenge to effective treatment. NO and reactive nitrogen species (RNS) are imperative antimicrobial components of the host immune response, which, when uncompromised, significantly diminish the risk of development of bacterial resistance.

Methods: We conducted a narrative review of the evidence underlying the antimicrobial mechanisms of NO and assessed its potential as an antimicrobial agent to treat hard-to-heal wounds.

Results: We identified and reviewed key antimicrobial mechanisms of NO and RNS. NO freely penetrates the bacterial cell wall and membrane, where RNS inactivates extracellular and internal cell wall proteins. RNS destroy microbial DNA while NO inhibits DNA synthesis and repair, destabilizing the genome resulting in cell disfunction and eventual death. RNS inactivate iron-sulfur cluster containing proteins that are essential to metabolic processes, resulting in bacterial cell death.

Discussion: NO generation within a wound dressing* represents a promising strategy as an antimicrobial agent for the treatment of hard-to-heal wounds, due to the multiple mechanisms of action of NOI, which reduce the risk of bacterial resistance.