Synergistic effect of immunomodulatory S100A8/A9 and ciprofloxacin against Pseudomonas aeruginosa biofilm in a murine chronic wound model. Issue 5 (22nd May 2019)

• Record Type: Journal Article
• Authors: Laulund, Anne Sofie Boe; Trøstrup, Hannah; Lerche, Christian Johann; Thomsen, Kim; Christophersen, Lars; Calum, Henrik; Høiby, Niels; Moser, Claus
• Is Part Of: Pathogens and disease. Volume 78:Issue 5(2020)
• Publication Date: 2019-05-22
• Subjects: biofilm -- flouroquinolone -- Pseudomonas; Medical microbiology -- Periodicals; Pathogenic microorganisms -- Periodicals; Communicable diseases -- Microbiology -- Periodicals; Communicable diseases -- Pathogenesis -- Periodicals; Host-parasite relationships -- Periodicals; Systems biology -- Periodicals; 616.904105
• DOI: 10.1093/femspd/ftz027
• Languages: English
• ISSNs: 2049-632X

Abstract

ABSTRACT: The majority of chronic wounds are associated with bacterial biofilms recalcitrant to antibiotics and host responses. Immunomodulatory S100A8/A9 is suppressed in Pseudomonas aeruginosa biofilm infected wounds. We aimed at investigating a possible additive effect between S100A8/A9 and ciprofloxacin against biofilms. Materials/methods: Thirty-two mice were injected with alginate-embedded P. aeruginosa following a third-degree burn. The mice were randomized into four groups receiving combination ciprofloxacin and S100A8/A9 or monotherapy ciprofloxacin, S100A8/A9 or a placebo and evaluated by host responses and quantitative bacteriology in wounds. In addition, in vitro checkerboard analysis was performed, with P. aeruginosa and ascending S100A8/A9 and ciprofloxacin concentrations. Results: S100A8/A9 augmented the effect of ciprofloxacin in vivo by lowering the bacterial quantity compared to the placebo arm and the two monointervention groups ( P < 0.0001). S100A8 and 100A9 were increased in the double-treated group as compared to the monointervention groups ( P = 0.032, P = 0.0023). Tissue inhibitor of metalloproteinases-1 and keratinocyte\chemokine chemoattractant-1 were increased in the double-intervention group compared to the S100A8/A9 group ( P = 0.050, P = 0.050). No in vitro synergism was detected. Conclusion: The observed ciprofloxacin-augmenting effect of S100A8/A9 in vivo was not confirmed by checkerboard analysis, indicating dependence on host cells for the S100A8/A9 effect. S100A8/A9 and ciprofloxacin is a promising therapy for optimizing chronic wound treatment. Abstract : Antibiotics combined with immunomodulating therapy lowers the bacterial load in biofilm-infected wounds.