Breaking the barrier – a novel approach to controlling infection in hard-to-heal wounds
Aims
This study aimed to evaluate anti-biofilm and wound healing effects of NX-AS-911 in an ex vivo wound model infected with ‘gold standard’ Pseudomonas aeruginosa and Staphylococcus aureus in the presence (and absence) of standard of care (SOC) antibiotics.
Methods
The anti-biofilm effects of NX-AS-911 on S aureus and
P aeruginosa in the presence (and absence) of SOC antibiotics were reviewed by inoculating artificial wounds 24- to 48-hours prior to a 3-day, daily treatment regime with NX-AS-911 in the presence and absence of SOC antibiotics. Sampling was performed day-2 and day-4 post initiating treatment. Analysis on the effect on total bioburden was performed through colony-forming units (CFU) determinations, followed by a review of the effects on pathogen and host gene expression through quantitative RT-PCR. Immuno-histochemical staining and microscopy were performed to evaluate the extent of epithelialisation/wound healing and presence of biofilm aggregates and inflammatory markers. Time points were day-4 and day-7 post initiating treatment.
Results
Treatment with NX-AS-911 increased the ex vivo efficacy of SOC antibiotics against S aureus and P aeruginosa biofilms. Expression of key pathogen virulence genes was reduced in the presence of NX-AS-911. Combination treatment also showed evidence of wound healing due to the reduction in pathogen virulence factor expression and bioburden and NX-AS-911 had an immuno-modulatory effect.
Conclusion
NX-AS-911 has anti-virulence activity against both S aureus and P aeruginosa. NX-AS-911 also enhanced the antibiotic activity of SOC antibiotics against clinically relevant strains of S aureus and P aeruginosa, supporting our efforts to progress this drug to clinical evaluation as an adjunctive therapy to conventional antibiotics in the treatment of chronic wound infections and cystic fibrosis.
Conflict of interest statement
There is no conflict of interest.
- © Royal College of Physicians 2019. All rights reserved.
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