Phage–Antibiotic–Peptide Synergy Overcomes Biofilm-Mediated Multidrug Resistance in Serratia marcescens

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Abstract
Background/Objectives: Serratia marcescens is an opportunistic pathogen that causes severe hospital-acquired infections, notable for its biofilm formation abilities and development of extensive antibiotic resistance. Here, we aim to evaluate the efficacy of bacteriophages, antibiotics, and antimicrobial peptides (BAP), alone and in combination, against fourteen multidrug-resistant (MDR) S. marcescens isolates sourced from hospitals and other environmental settings. Methods: S. marcescens was grown planktonically or in surface-associated biofilms, and biofilm biomass was measured via changes in absorbance and colony-forming units or live/death staining. Results: Combining bacteriophage with a low-dose cocktail of penicillin–streptomycin, kanamycin, and ciprofloxacin enhanced antimicrobial activity compared with antibiotics alone. Across the isolate panel, responses to BAP treatment varied according to determined antibiotic resistance profiles. The highly resistant AR-0517 isolate was selected for detailed mature biofilm analysis, where the BAP treatment reduced biofilm biomass by 97.8% and recoverable bacteria by 99.99%. Microscopy and viability assays further confirmed extensive biofilm disruption and bacterial killing. Conclusions: These findings demonstrate that simultaneous targeting of multiple bacterial pathways can enhance antimicrobial activity against MDR S. marcescens in vitro and support further evaluation of BAP as a potential strategy for biofilm-associated infections.
Funding Information
  • Centers for Disease Control and Prevention (U54CK000603)
  • National Institutes of Health National Institute of Allergy and Infectious Diseases (R01 AI168313)
  • University of Maryland College Park Start-up Funds

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