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The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Synergistic effect of immunomodulatory S100A8/A9 and ciprofloxacin against Pseudomonas aeruginosa biofilm in a murine chronic wound model

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The majority of chronic wounds are associated with bacterial biofilms recalcitrant to antibiotics and host responses.Immunomodulatory S100A8/A9 is suppressed in P. aeruginosa biofilms 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. Mice were randomized into four groups receiving combination ciprofloxacin and S100A8/A9 or monotherapy ciprofloxacin, S100A8/A9 or placebo. 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 bacterial quantity compared to the placebo arm and the two mono-intervention groups (P < 0.0001).S100A8 and 100A9 were increased in the double-treated group as compared to the mono-intervention groups (P = 0.032, P = 0.0023). TIMP-1 and KC/CXCL-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 of host cells for the S100A8/A9 effect. S100A8/A9 and ciprofloxacin is a promising therapy for optimizing chronic wound treatment.

Original languageEnglish
JournalPathogens and Disease
ISSN2049-632X
DOIs
Publication statusE-pub ahead of print - 2020

ID: 57229715