Substrate morphology modulates bacteriophage mobility and alters bactericidal potency
6 affiliations
- 1School of Engineering and Physical Sciences, University of Lincoln, Lincoln, United Kingdom
- 2School of Agri‐Food Technology and Manufacturing, University of Lincoln, Holbeach, United Kingdom
- 3Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
- 4School of Engineering & Technology, Duy Tan University, Da Nang, Vietnam
- 5Biomedical Engineering Research Group, School of Engineering, University of Leicester, Leicester, United Kingdom
- 6Division of Surgery & Interventional Science, University College London, Royal National Orthopaedic Hospital, London, United Kingdom
Abstract
Bacteriophages (phages) are regaining attention as alternatives to antibiotics in the antimicrobial resistance crisis. Although successful cases are widely reported, the influence of physical, abiotic substrate morphology on phage performance remains largely unexamined, despite morphology being an intrinsic topographical feature present at many infection and decontamination sites, such as granular chronic wound beds or porous bone-implant interfaces. In this study, smooth, rough, and porous substrates were physically engineered to investigate the effects of abiotic substrate morphology on phage potency. Profiler and SEM analyses confirmed three distinct morphologies spanning several orders of magnitude in surface roughness. Phage K exhibited a clear hierarchy of bactericidal activity across these morphologies, with the highest activity on smooth substrates, reduced activity on rough substrates, and the lowest activity on porous architectures. Histological analysis and COMSOL simulations revealed that increasing morphological complexity elevates tortuosity and reduces phage accessibility and the probability of encountering pathogens. Together, these findings establish substrate morphology as a critical determinant of phage kinetics and bactericidal potency, relevant both to surface decontamination and, cautiously, to real infection sites such as wound beds and implant-tissue interfaces that inherently possess complex microarchitectures. Incorporating substrate morphology into the design of phage-based applications may improve the predictive accuracy of dosing, interval design, and clinical translation, and deepen understanding of the underlying pharmacology.
Related
- Glutamate-Induced AMPA Receptor Desensitization Increases Their Mobility and Modulates Short-Term Plasticity through Unbinding from Stargazin
- Auranofin shows bactericidal activity in Pseudomonas aeruginosa by targeting thiol homeostasis
- A moonlighting serpin of Tannerella forsythia compromises the bactericidal activity of neutrophils
- Mucosal ACP subunit vaccine formulated with a small molecule STING agonist drives protective TH1/TH17 responses and serum bactericidal antibodies against Neisseria gonorrhoeae
- Geographical variation in plasma bactericidal ability of breeding tree swallows (Tachycineta bicolor)
BibTeX
@article{wang2026substrate,
title = {{Substrate morphology modulates bacteriophage mobility and alters bactericidal potency}},
author = {Haoyu Wang and Oluyemi Olatunji Awolusi and Saravana Kumar Jaganathan and Jing Lyu and Chaozong Liu and Nick Tucker and Bukola Adenike Onarinde},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0356919},
url = {https://doi.org/10.1371/journal.pone.0356919},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Substrate morphology modulates bacteriophage mobility and alters bactericidal potency
AU - Haoyu Wang
AU - Oluyemi Olatunji Awolusi
AU - Saravana Kumar Jaganathan
AU - Jing Lyu
AU - Chaozong Liu
AU - Nick Tucker
AU - Bukola Adenike Onarinde
PY - 2026
DA - 2026/09/16
JO - PLOS One
DO - 10.1371/journal.pone.0356919
UR - https://doi.org/10.1371/journal.pone.0356919
AB - Bacteriophages (phages) are regaining attention as alternatives to antibiotics in the antimicrobial resistance crisis. Although successful cases are widely reported, the influence of physical, abiotic substrate morphology on phage performance remains largely unexamined, despite morphology being an intrinsic topographical feature present at many infection and decontamination sites, such as granular chronic wound beds or porous bone-implant interfaces. In this study, smooth, rough, and porous substrates were physically engineered to investigate the effects of abiotic substrate morphology on phage potency. Profiler and SEM analyses confirmed three distinct morphologies spanning several orders of magnitude in surface roughness. Phage K exhibited a clear hierarchy of bactericidal activity across these morphologies, with the highest activity on smooth substrates, reduced activity on rough substrates, and the lowest activity on porous architectures. Histological analysis and COMSOL simulations revealed that increasing morphological complexity elevates tortuosity and reduces phage accessibility and the probability of encountering pathogens. Together, these findings establish substrate morphology as a critical determinant of phage kinetics and bactericidal potency, relevant both to surface decontamination and, cautiously, to real infection sites such as wound beds and implant-tissue interfaces that inherently possess complex microarchitectures. Incorporating substrate morphology into the design of phage-based applications may improve the predictive accuracy of dosing, interval design, and clinical translation, and deepen understanding of the underlying pharmacology.
SN - 1932-6203
ER -