Lactoferricin-inspired peptide AMC-109 augments the effect of ciprofloxacin against Pseudomonas aeruginosa biofilm in chronic murine wounds
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Objectives: Chronic wounds are characterised by prolonged inflammation, low mitogenic activity, high protease/low inhibitor activity, microbiota changes and biofilm formation, combined with the aetiology of the original insult. One strategy to promote healing is to terminate the parasitism-like relationship between the biofilm-growing pathogen and host response. Antimicrobial peptide AMC-109 is a potential treatment with low resistance potential and broad-spectrum coverage with rapid bactericidal effect. We aimed to investigate whether adjunctive AMC-109 could augment the ciprofloxacin effect in a chronic Pseudomonas aeruginosa wound model. Methods: Third-degree burns were inflicted on 33 BALB/c mice. Pseudomonas aeruginosa embedded in seaweed alginate was injected sub-eschar to mimic biofilm. Mice were randomised to receive AMC-109, combined AMC-109 and ciprofloxacin, ciprofloxacin, or placebo for 5 days followed by sample collection. Results: A lower bacterial load was seen in the double-treated group compared with either monotherapy group (AMC-109, p = 0.0076; ciprofloxacin, p = 0.0266). To evaluate the innate host response, cytokines and growth factors were quantified. The pro-inflammatory response was dampened in the double-treated mice compared with the mono-ciprofloxacin-treated group (p = 0.0009). Lower mobilisation of neutrophils from the bone marrow was indicated by reduced G-CSF in all treatment groups compared with placebo. Improved tissue remodelling was indicated by the highest level of tissue inhibitor of metalloproteases and low metalloprotease level in the double-treated group. Conclusion: AMC-109 showed adjunctive antipseudomonal abilities augmenting the antimicrobial effect of ciprofloxacin in this wound model. The study indicates a potential role for AMC-109 in treating chronic wounds with complicating biofilm infections.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Global Antimicrobial Resistance |
Vol/bind | 29 |
Sider (fra-til) | 185-193 |
Antal sider | 9 |
ISSN | 2213-7165 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
Raw data are available by contacting the corresponding author. CM has received the 5-year ?Borregaard Clinical Ascending Investigator? by the Novo Nordisk Foundation [NNF17OC0025074]. ASL has received a full PhD scholarship from Rigshospitalet Research Committee [E-22416-05]. The funders had no influence on the planning of the study or interpretation of the data. JSMS and JPC are employed by Amicoat AS. All other authors declare no competing interests. The in vivo experiment was approved by the Danish Animal Experiments Inspectorate [approval no. 2015-15-0201-00618]. The experiment complied with the ARRIVE guidelines and was carried out in accordance with the UK Animals (Scientific Procedures) Act 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments.
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© 2022 The Authors
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