3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation

Frits van Charante; David Martínez-Pérez; Clara Guarch-Pérez; Charlotte Courtens; Andrea Sass; Emilia Choińska; Joanna Idaszek; Serge van Calenbergh; Martijn Riool; Sebastian A. J. Zaat; Wojciech Święszkowski; Tom Coenye

doi:https://doi.org/10.1016/j.isci.2023.107557

3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation

Frits van Charante, David Martínez-Pérez, Clara Guarch-Pérez, Charlotte Courtens, Andrea Sass, Emilia Choińska, Joanna Idaszek, Serge van Calenbergh, Martijn Riool, Sebastian A. J. Zaat, Wojciech Święszkowski, Tom Coenye

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Acinetobacter baumannii causes a wide range of infections, including wound infections. Multidrug-resistant A. baumannii is a major healthcare concern and the development of novel treatments against these infections is needed. Fosmidomycin is a repurposed antimalarial drug targeting the non-mevalonate pathway, and several derivatives show activity toward A. baumannii. We evaluated the antimicrobial activity of CC366, a fosmidomycin prodrug, against a collection of A. baumannii strains, using various in vitro and in vivo models; emphasis was placed on the evaluation of its anti-biofilm activity. We also developed a 3D-printed wound dressing containing CC366, using melt electrowriting technology. Minimal inhibitory concentrations of CC366 ranged from 1 to 64 μg/mL, and CC366 showed good biofilm inhibitory and moderate biofilm eradicating activity in vitro. CC366 successfully eluted from a 3D-printed dressing, the dressings prevented the formation of A. baumannnii wound biofilms in vitro and reduced A. baumannii infection in an in vivo mouse model.

Original language	English
Article number	107557
Journal	iScience
Volume	26
Issue number	9
DOIs	https://doi.org/10.1016/j.isci.2023.107557
Publication status	Published - 15 Sept 2023

Keywords

Microbiofilms
Microbiology

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https://doi.org/10.1016/j.isci.2023.107557

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van Charante, F., Martínez-Pérez, D., Guarch-Pérez, C., Courtens, C., Sass, A., Choińska, E., Idaszek, J., van Calenbergh, S., Riool, M., Zaat, S. A. J., Święszkowski, W., & Coenye, T. (2023). 3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation. iScience, 26(9), Article 107557. https://doi.org/10.1016/j.isci.2023.107557

@article{f31764b6e871470385cdcb9cba68f706,

title = "3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation",

abstract = "Acinetobacter baumannii causes a wide range of infections, including wound infections. Multidrug-resistant A. baumannii is a major healthcare concern and the development of novel treatments against these infections is needed. Fosmidomycin is a repurposed antimalarial drug targeting the non-mevalonate pathway, and several derivatives show activity toward A. baumannii. We evaluated the antimicrobial activity of CC366, a fosmidomycin prodrug, against a collection of A. baumannii strains, using various in vitro and in vivo models; emphasis was placed on the evaluation of its anti-biofilm activity. We also developed a 3D-printed wound dressing containing CC366, using melt electrowriting technology. Minimal inhibitory concentrations of CC366 ranged from 1 to 64 μg/mL, and CC366 showed good biofilm inhibitory and moderate biofilm eradicating activity in vitro. CC366 successfully eluted from a 3D-printed dressing, the dressings prevented the formation of A. baumannnii wound biofilms in vitro and reduced A. baumannii infection in an in vivo mouse model.",

keywords = "Microbiofilms, Microbiology",

author = "{van Charante}, Frits and David Mart{\'i}nez-P{\'e}rez and Clara Guarch-P{\'e}rez and Charlotte Courtens and Andrea Sass and Emilia Choi{\'n}ska and Joanna Idaszek and {van Calenbergh}, Serge and Martijn Riool and Zaat, {Sebastian A. J.} and Wojciech {\'S}wi{\c e}szkowski and Tom Coenye",

note = "Funding Information: This work was funded by the EU within the EU Framework Programme for Research and Innovation Horizon 2020—Marie Sk{\l}odowska-Curie Innovative Training Networks (grant agreements No. 722467 and 860816 ; research projects PRINT-AID and MepAnti, respectively) and EU H2020-WIDESPREAD-05-2020 —Twinning grant CEMBO (number 952398 ). Additional funding was obtained from the Special Research Fund of Ghent University (grants BOF20-GOA002 and BOFITN-2020 ). C.C. thanks the Research Foundation—Flanders (FWO) for a PhD-scholarship (1121315N). Funding Information: We thank H. Goossens, Y. Briers, B. Verhasselt, and C. Van der Henst for providing strains. We would like to thank the animal caretakers of the Animal Research Institute (ARIA, Amsterdam UMC, The Netherlands) for their excellent support during the animal experiments and Nicole van der Wel (Electron Microscopy Center Amsterdam, Amsterdam UMC, The Netherlands) for her technical assistance with SEM. We thank the Oxford Genomics Center at the Wellcome Center for Human Genetics (funded by Wellcome Trust grant ref. 203141/Z/16/Z ) for the generation and initial processing of the whole genome sequencing data. Funding Information: This work was funded by the EU within the EU Framework Programme for Research and Innovation Horizon 2020—Marie Sk{\l}odowska-Curie Innovative Training Networks (grant agreements No. 722467 and 860816; research projects PRINT-AID and MepAnti, respectively) and EU H2020-WIDESPREAD-05-2020—Twinning grant CEMBO (number 952398). Additional funding was obtained from the Special Research Fund of Ghent University (grants BOF20-GOA002 and BOFITN-2020). C.C. thanks the Research Foundation—Flanders (FWO) for a PhD-scholarship (1121315N). We thank H. Goossens, Y. Briers, B. Verhasselt, and C. Van der Henst for providing strains. We would like to thank the animal caretakers of the Animal Research Institute (ARIA, Amsterdam UMC, The Netherlands) for their excellent support during the animal experiments and Nicole van der Wel (Electron Microscopy Center Amsterdam, Amsterdam UMC, The Netherlands) for her technical assistance with SEM. We thank the Oxford Genomics Center at the Wellcome Center for Human Genetics (funded by Wellcome Trust grant ref. 203141/Z/16/Z) for the generation and initial processing of the whole genome sequencing data. Conceptualization, T.C. S.A.J.Z. M.R. and W.S.; Methodology, F.v.C. D.M.P. and C.G.P.; Formal Analysis, T.C. F.v.C. D.M.P. C.G.P. and M.R.; Investigation, F.v.C. D.M.P. C.G.P. C.C. J.S. A.S. E.C. and M.R.; Writing – Original Draft, F.v.C, D.M.P, C.G.P, and T.C.; Writing – Review and Editing, all authors; Supervision: T.C. S.V.C. M.R. S.A.Z.J. and W.S.; Project Administration, T.C. M.R. S.A.Z.J. and W.S.; Funding Acquisition, T.C. S.A.Z.J. and W.S. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = sep,

day = "15",

doi = "https://doi.org/10.1016/j.isci.2023.107557",

language = "English",

volume = "26",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier",

number = "9",

}

van Charante, F, Martínez-Pérez, D, Guarch-Pérez, C, Courtens, C, Sass, A, Choińska, E, Idaszek, J, van Calenbergh, S, Riool, M , Zaat, SAJ, Święszkowski, W & Coenye, T 2023, '3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation', iScience, vol. 26, no. 9, 107557. https://doi.org/10.1016/j.isci.2023.107557

TY - JOUR

T1 - 3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation

AU - van Charante, Frits

AU - Martínez-Pérez, David

AU - Guarch-Pérez, Clara

AU - Courtens, Charlotte

AU - Sass, Andrea

AU - Choińska, Emilia

AU - Idaszek, Joanna

AU - van Calenbergh, Serge

AU - Riool, Martijn

AU - Zaat, Sebastian A. J.

AU - Święszkowski, Wojciech

AU - Coenye, Tom

N1 - Funding Information: This work was funded by the EU within the EU Framework Programme for Research and Innovation Horizon 2020—Marie Skłodowska-Curie Innovative Training Networks (grant agreements No. 722467 and 860816 ; research projects PRINT-AID and MepAnti, respectively) and EU H2020-WIDESPREAD-05-2020 —Twinning grant CEMBO (number 952398 ). Additional funding was obtained from the Special Research Fund of Ghent University (grants BOF20-GOA002 and BOFITN-2020 ). C.C. thanks the Research Foundation—Flanders (FWO) for a PhD-scholarship (1121315N). Funding Information: We thank H. Goossens, Y. Briers, B. Verhasselt, and C. Van der Henst for providing strains. We would like to thank the animal caretakers of the Animal Research Institute (ARIA, Amsterdam UMC, The Netherlands) for their excellent support during the animal experiments and Nicole van der Wel (Electron Microscopy Center Amsterdam, Amsterdam UMC, The Netherlands) for her technical assistance with SEM. We thank the Oxford Genomics Center at the Wellcome Center for Human Genetics (funded by Wellcome Trust grant ref. 203141/Z/16/Z ) for the generation and initial processing of the whole genome sequencing data. Funding Information: This work was funded by the EU within the EU Framework Programme for Research and Innovation Horizon 2020—Marie Skłodowska-Curie Innovative Training Networks (grant agreements No. 722467 and 860816; research projects PRINT-AID and MepAnti, respectively) and EU H2020-WIDESPREAD-05-2020—Twinning grant CEMBO (number 952398). Additional funding was obtained from the Special Research Fund of Ghent University (grants BOF20-GOA002 and BOFITN-2020). C.C. thanks the Research Foundation—Flanders (FWO) for a PhD-scholarship (1121315N). We thank H. Goossens, Y. Briers, B. Verhasselt, and C. Van der Henst for providing strains. We would like to thank the animal caretakers of the Animal Research Institute (ARIA, Amsterdam UMC, The Netherlands) for their excellent support during the animal experiments and Nicole van der Wel (Electron Microscopy Center Amsterdam, Amsterdam UMC, The Netherlands) for her technical assistance with SEM. We thank the Oxford Genomics Center at the Wellcome Center for Human Genetics (funded by Wellcome Trust grant ref. 203141/Z/16/Z) for the generation and initial processing of the whole genome sequencing data. Conceptualization, T.C. S.A.J.Z. M.R. and W.S.; Methodology, F.v.C. D.M.P. and C.G.P.; Formal Analysis, T.C. F.v.C. D.M.P. C.G.P. and M.R.; Investigation, F.v.C. D.M.P. C.G.P. C.C. J.S. A.S. E.C. and M.R.; Writing – Original Draft, F.v.C, D.M.P, C.G.P, and T.C.; Writing – Review and Editing, all authors; Supervision: T.C. S.V.C. M.R. S.A.Z.J. and W.S.; Project Administration, T.C. M.R. S.A.Z.J. and W.S.; Funding Acquisition, T.C. S.A.Z.J. and W.S. The authors declare no competing interests. Publisher Copyright: © 2023 The Authors

PY - 2023/9/15

Y1 - 2023/9/15

N2 - Acinetobacter baumannii causes a wide range of infections, including wound infections. Multidrug-resistant A. baumannii is a major healthcare concern and the development of novel treatments against these infections is needed. Fosmidomycin is a repurposed antimalarial drug targeting the non-mevalonate pathway, and several derivatives show activity toward A. baumannii. We evaluated the antimicrobial activity of CC366, a fosmidomycin prodrug, against a collection of A. baumannii strains, using various in vitro and in vivo models; emphasis was placed on the evaluation of its anti-biofilm activity. We also developed a 3D-printed wound dressing containing CC366, using melt electrowriting technology. Minimal inhibitory concentrations of CC366 ranged from 1 to 64 μg/mL, and CC366 showed good biofilm inhibitory and moderate biofilm eradicating activity in vitro. CC366 successfully eluted from a 3D-printed dressing, the dressings prevented the formation of A. baumannnii wound biofilms in vitro and reduced A. baumannii infection in an in vivo mouse model.

AB - Acinetobacter baumannii causes a wide range of infections, including wound infections. Multidrug-resistant A. baumannii is a major healthcare concern and the development of novel treatments against these infections is needed. Fosmidomycin is a repurposed antimalarial drug targeting the non-mevalonate pathway, and several derivatives show activity toward A. baumannii. We evaluated the antimicrobial activity of CC366, a fosmidomycin prodrug, against a collection of A. baumannii strains, using various in vitro and in vivo models; emphasis was placed on the evaluation of its anti-biofilm activity. We also developed a 3D-printed wound dressing containing CC366, using melt electrowriting technology. Minimal inhibitory concentrations of CC366 ranged from 1 to 64 μg/mL, and CC366 showed good biofilm inhibitory and moderate biofilm eradicating activity in vitro. CC366 successfully eluted from a 3D-printed dressing, the dressings prevented the formation of A. baumannnii wound biofilms in vitro and reduced A. baumannii infection in an in vivo mouse model.

KW - Microbiofilms

KW - Microbiology

UR - http://www.scopus.com/inward/record.url?scp=85169589833&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.isci.2023.107557

DO - https://doi.org/10.1016/j.isci.2023.107557

M3 - Article

C2 - 37680458

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 9

M1 - 107557

ER -

3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation

Abstract

Keywords

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