Cellular heterogeneity in the response of Burkholderia thailandensis to antibiotics and phages in synthetic spatial refuges
- 1University of Exeter
Abstract
Understanding the complex interactions between phage, antibiotics and bacteria is vital for the development of rationale phage-antibiotic therapies. These interactions have traditionally been investigated via bulk assays, thus masking eventual cellular heterogeneities and the impact of spatial refuges on phage and antibiotic efficacy. Using microfluidics-based time-lapse microscopy, we reveal large phenotypic heterogeneity in the response of Burkholderia thailandensis to both the bacteriophage {Phi}Bp-AMP1 and sub-inhibitory concentrations of two selected antibiotics ciprofloxacin and trimethoprim. We discover that simultaneous exposure to ciprofloxacin and phage decreases the size of individual B. thailandensis cells, whereas phage and trimethoprim together slow down cell doubling. Exposure to ciprofloxacin also causes extended phage lysis of B. thailandensis which is preceded by a distinguishable pause in cell elongation, whereas exposure to trimethoprim constrains lysis. As a consequence, exposure to ciprofloxacin further hinders the growth of B. thailandensis in the presence of phage, whereas exposure to trimethoprim enhances growth in the presence of phage. These findings help understand the effects of the interactions between antibiotics and phage on bacterial subpopulations in spatial refuges that are notoriously difficult to treat with antibiotics.
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BibTeX
@misc{kraus2026cellular,
title = {{Cellular heterogeneity in the response of Burkholderia thailandensis to antibiotics and phages in synthetic spatial refuges}},
author = {S. Kraus and M. L. Fletcher and U. Lapinska and S. Korbsrisate and S. V. Harding and K. Tsaneva-Atanasova and M. A. T. Blaskovich and S. Pagliara},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.26.754594},
url = {https://www.biorxiv.org/content/10.64898/2026.09.26.754594v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cellular heterogeneity in the response of Burkholderia thailandensis to antibiotics and phages in synthetic spatial refuges
AU - S. Kraus
AU - M. L. Fletcher
AU - U. Lapinska
AU - S. Korbsrisate
AU - S. V. Harding
AU - K. Tsaneva-Atanasova
AU - M. A. T. Blaskovich
AU - S. Pagliara
PY - 2026
DA - 2026/09/26
PB - bioRxiv
DO - 10.64898/2026.09.26.754594
UR - https://www.biorxiv.org/content/10.64898/2026.09.26.754594v1
AB - Understanding the complex interactions between phage, antibiotics and bacteria is vital for the development of rationale phage-antibiotic therapies. These interactions have traditionally been investigated via bulk assays, thus masking eventual cellular heterogeneities and the impact of spatial refuges on phage and antibiotic efficacy. Using microfluidics-based time-lapse microscopy, we reveal large phenotypic heterogeneity in the response of Burkholderia thailandensis to both the bacteriophage {Phi}Bp-AMP1 and sub-inhibitory concentrations of two selected antibiotics ciprofloxacin and trimethoprim. We discover that simultaneous exposure to ciprofloxacin and phage decreases the size of individual B. thailandensis cells, whereas phage and trimethoprim together slow down cell doubling. Exposure to ciprofloxacin also causes extended phage lysis of B. thailandensis which is preceded by a distinguishable pause in cell elongation, whereas exposure to trimethoprim constrains lysis. As a consequence, exposure to ciprofloxacin further hinders the growth of B. thailandensis in the presence of phage, whereas exposure to trimethoprim enhances growth in the presence of phage. These findings help understand the effects of the interactions between antibiotics and phage on bacterial subpopulations in spatial refuges that are notoriously difficult to treat with antibiotics.
ER -