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

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@article{d933b465e6924846a07ac82d2103c8f4,
title = "Synergistic effect of immunomodulatory S100A8/A9 and ciprofloxacin against Pseudomonas aeruginosa biofilm in a murine chronic wound model",
abstract = "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.",
author = "Laulund, {Anne Sofie Boe} and Hannah Tr{\o}strup and Lerche, {Christian Johann} and Kim Thomsen and Lars Christophersen and Henrik Calum and Niels H{\o}iby and Claus Moser",
note = "{\circledC} FEMS 2019.",
year = "2019",
month = "5",
day = "22",
doi = "10.1093/femspd/ftz027",
language = "English",
journal = "Pathogens and Disease",
issn = "2049-632X",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Synergistic effect of immunomodulatory S100A8/A9 and ciprofloxacin against Pseudomonas aeruginosa biofilm in a murine chronic wound model

AU - Laulund, Anne Sofie Boe

AU - Trøstrup, Hannah

AU - Lerche, Christian Johann

AU - Thomsen, Kim

AU - Christophersen, Lars

AU - Calum, Henrik

AU - Høiby, Niels

AU - Moser, Claus

N1 - © FEMS 2019.

PY - 2019/5/22

Y1 - 2019/5/22

N2 - 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.

AB - 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.

U2 - 10.1093/femspd/ftz027

DO - 10.1093/femspd/ftz027

M3 - Journal article

JO - Pathogens and Disease

JF - Pathogens and Disease

SN - 2049-632X

ER -

ID: 57229715