Antibiotic carry over is a confounding factor for cell-based antimicrobial research applications

Abstract Chronic wounds often host pathogens like Staphylococcus aureus, prompting interest in developing new antimicrobial and wound healing strategies, including the utilisation of extracellular vesicles (EVs). Whilst there has been a recent emphasis within the EV community to ensure standardizati...

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Main Authors: Miran Yousri Elfar, Helen Louise Brown, Aled Clayton, Phil Stephens
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-14186-7
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author Miran Yousri Elfar
Helen Louise Brown
Aled Clayton
Phil Stephens
author_facet Miran Yousri Elfar
Helen Louise Brown
Aled Clayton
Phil Stephens
author_sort Miran Yousri Elfar
collection DOAJ
description Abstract Chronic wounds often host pathogens like Staphylococcus aureus, prompting interest in developing new antimicrobial and wound healing strategies, including the utilisation of extracellular vesicles (EVs). Whilst there has been a recent emphasis within the EV community to ensure standardization of characterization and isolation techniques, there has been less focus placed on the upstream tissue culture methodologies used for collection of vesicle-containing conditioned medium (CM). Hence, this study investigated the antimicrobial properties of the CM used for EV enrichment. CM exhibited bacteriostatic effects against penicillin-sensitive S. aureus NCTC 6571, but not penicillin-resistant S. aureus 1061 A. Further analysis revealed that the antimicrobial activity was due to residual antibiotics rather than cell-secreted factors, specifically the retention and release of penicillin to tissue culture plastic surfaces. Pre-washing cells and minimizing antibiotic concentrations in basal medium reduced this carry-over effect. These findings emphasize the importance of controlling antibiotic use in tissue culture to avoid misleading conclusions about the antimicrobial potential of CM or EVs. Researchers should carefully consider medium selection and supplementation during method development as accurately determining the antimicrobial mechanisms of any CM is essential for validating future cell-based therapeutic applications.
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spelling doaj-art-def0b0b62dd04c8f89b7d5792da5ac882025-08-20T03:05:17ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-14186-7Antibiotic carry over is a confounding factor for cell-based antimicrobial research applicationsMiran Yousri Elfar0Helen Louise Brown1Aled Clayton2Phil Stephens3School of Dentistry, Cardiff UniversitySchool of Biosciences, Cardiff UniversityDivision of Cancer & Genetics, School of MedicineSchool of Dentistry, Cardiff UniversityAbstract Chronic wounds often host pathogens like Staphylococcus aureus, prompting interest in developing new antimicrobial and wound healing strategies, including the utilisation of extracellular vesicles (EVs). Whilst there has been a recent emphasis within the EV community to ensure standardization of characterization and isolation techniques, there has been less focus placed on the upstream tissue culture methodologies used for collection of vesicle-containing conditioned medium (CM). Hence, this study investigated the antimicrobial properties of the CM used for EV enrichment. CM exhibited bacteriostatic effects against penicillin-sensitive S. aureus NCTC 6571, but not penicillin-resistant S. aureus 1061 A. Further analysis revealed that the antimicrobial activity was due to residual antibiotics rather than cell-secreted factors, specifically the retention and release of penicillin to tissue culture plastic surfaces. Pre-washing cells and minimizing antibiotic concentrations in basal medium reduced this carry-over effect. These findings emphasize the importance of controlling antibiotic use in tissue culture to avoid misleading conclusions about the antimicrobial potential of CM or EVs. Researchers should carefully consider medium selection and supplementation during method development as accurately determining the antimicrobial mechanisms of any CM is essential for validating future cell-based therapeutic applications.https://doi.org/10.1038/s41598-025-14186-7Chronic woundChronic wound infectionFibroblastStaphylococcus aureusBiofilm
spellingShingle Miran Yousri Elfar
Helen Louise Brown
Aled Clayton
Phil Stephens
Antibiotic carry over is a confounding factor for cell-based antimicrobial research applications
Scientific Reports
Chronic wound
Chronic wound infection
Fibroblast
Staphylococcus aureus
Biofilm
title Antibiotic carry over is a confounding factor for cell-based antimicrobial research applications
title_full Antibiotic carry over is a confounding factor for cell-based antimicrobial research applications
title_fullStr Antibiotic carry over is a confounding factor for cell-based antimicrobial research applications
title_full_unstemmed Antibiotic carry over is a confounding factor for cell-based antimicrobial research applications
title_short Antibiotic carry over is a confounding factor for cell-based antimicrobial research applications
title_sort antibiotic carry over is a confounding factor for cell based antimicrobial research applications
topic Chronic wound
Chronic wound infection
Fibroblast
Staphylococcus aureus
Biofilm
url https://doi.org/10.1038/s41598-025-14186-7
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AT philstephens antibioticcarryoverisaconfoundingfactorforcellbasedantimicrobialresearchapplications