ArticleJournal of biomedical science2026
Phage-antibiotic synergy restores β-lactam efficacy in MDR Klebsiella quasipneumoniae biofilms and suppresses resistance.
Article in Journal of biomedical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- A comprehensive phage-bacteria interaction atlas links phage lineage and capsule serotype to genome-guided machine learning prediction inbioRxiv : the preprint server for biology · 2026Article
- Antibacterial and antibiofilm effects of natural phenolic acids: Insights into structure-function relationships, extracellular pH, and morphological changes.Microbiology spectrum · 2026Article
- Bacteriophages in the environmental control of antimicrobial resistance: opportunities, risks, and surveillance challenges.Frontiers in microbiology · 2026Review
- Phage-antibiotic synergy attenuatesFrontiers in cellular and infection microbiology · 2026Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundBiofilms formed by multidrug-resistant (MDR) Klebsiella spp. present a significant clinical challenge due to elevated antibiotic tolerance. Bacteriophages (phages) represent a promising alternative, particularly in combination with antibiotics, where phage-antibiotic synergy (PAS) can increase antibiofilm activity. Evaluating treatment efficacy in these complex structures requires real-time, noninvasive viability analysis.
methodsTo address this, we used light-sheet fluorescence microscopy (LSFM), a high-resolution, minimally invasive approach, for dynamic tracking of PAS in intact biofilms. To our knowledge, this is the first in vitro application of LSFM for investigating PAS. We studied the combined activity of a virulent phage (vB_KpUKJ_2) and ceftazidime (CAZ) against an extended-spectrum β-lactamase-producing Klebsiella quasipneumoniae.
resultsIn planktonic cultures, PAS was strongly affected in a dose-dependent manner. In mature biofilms, LSFM imaging revealed that high-dose phages (10⁸ PFU/mL) combined with CAZ at a 0.25 × minimum inhibitory concentration (MIC) induced a rapid and sustained reduction in viability over 24 h. This regimen significantly outperformed mono-treatments (p < 0.01), demonstrating that phage coadministration can reduce the required antibiotic dose. Mechanistically, treatment resulted in phage-mediated degradation of α- and β-polysaccharides within the extracellular polymeric substance (EPS). Crucially, while phage mono-treatment led to the emergence of resistant mutants, the combination treatment fully suppressed resistance. Whole-genome sequencing revealed mutations in genes such as fhuA, purA, and rpoC, suggesting diverse resistance mechanisms linked to fitness trade-offs such as impaired biofilm formation.
conclusionsOur findings highlight a precision-guided strategy with translational potential for device-associated infections, providing a mechanistic and methodological foundation for optimizing PAS-based therapies.
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