The Pathogenesis of Treatment Resistance and the Role of Hypochlorous Acid (HOCl)
Antimicrobial resistance is one of the greatest challenges facing modern veterinary medicine. Chronically recurring infections and clinical stagnation are frequently observed in veterinary practice.
The reason for the lack of therapeutic success often lies in the way pathogens organize themselves: they form a biofilm.
What is a biofilm?
A biofilm is an organized community of microorganisms embedded in an extracellular matrix (EPS) that they produce themselves. This matrix consists of polysaccharides, proteins, and extracellular DNA, and effectively protects bacteria from external influences.
Formation of a mature biofilm
How Tolerance Mechanisms Develop
Bacteria within a mature biofilm exhibit greater tolerance to antibiotics and conventional antiseptics than their free-floating precursors. This resistance is based primarily on three mechanisms:
- Diffusion barrier: The negatively charged EPS matrix acts as a filter. Large or highly charged active ingredients cannot penetrate
- Metabolic inactivity: Due to oxygen and nutrient gradients, bacteria in the deeper layers are in a state of reduced metabolic activity. Since most antibiotics interfere with active cellular processes, they have little effect here.
- Horizontal gene transfer: The density within the biofilm facilitates the exchange of resistance genes between bacterial species.
Hypochlorous acid (HOCl): Mechanism of action in biofilms
Hypochlorous acid is a naturally occurring molecule produced by neutrophils as part of the body’s natural immune defense.
The effectiveness of hypochlorous acid in treating biofilms can be attributed to its physicochemical properties.
HOCl is electrically neutral and therefore does not experience electrostatic repulsion or binding to the negatively charged EPS matrix. This allows for unimpeded diffusion into deeper layers.
As soon as HOCl comes into contact with the bacterial cell, it causes oxidation in bacterial proteins, thereby inducing apoptosis. More highly developed eukaryotic cells possess more complex protective mechanisms, which is why HOCl exhibits good tissue compatibility at concentrations appropriate for clinical use and does not attack granulation tissue.
Practical Implications
In veterinary medicine, biofilms are a major cause of chronic and treatment-resistant infections. Especially in an era of increasing antibiotic resistance, the local control of microbial contamination is becoming increasingly important.
Hypochlorous acid offers a new approach here: it is effective against biofilms, gentle on tissues, and has no known potential for resistance.
This opens up an additional opportunity for veterinarians to align modern wound and skin therapies more closely with biofilm management and antibiotic stewardship.
Sources:
Robson MC, Payne WG, Ko F, Mentis M, Donati G, Shafii SM, Culverhouse S, Wang L, Khosrovi B, Najafi R, Cooper DM, Bassiri M. Hypochlorous Acid as a Potential Wound Care Agent: Part II. Stabilized Hypochlorous Acid: Its Role in Decreasing Tissue Bacterial Bioburden and Overcoming the Inhibition of Infection on Wound Healing. J Burns Wounds. 2007 Apr 11;6:e6. PMID: 17492051; PMCID: PMC1853324.
S.J. Westgate, S.L. Percival, D.C. Knottenbelt, P.D. Clegg, C.A. Cochrane, Microbiology of equine wounds and evidence of bacterial biofilms, Veterinary Microbiology, Volume 150, Issues 1–2, 2011, Pages 152-159, ISSN 0378-1135, https://doi.org/10.1016/j.vetmic.2011.01.003.