A Triple-Modality Peptide-Antibiotic-Phage Therapy Eradicates Multidrug-Resistant Serratia marcescens Biofilms

Area of Science:

• Microbiology
• Infectious Diseases
• Biotechnology

Background:

• Serratia marcescens is an opportunistic pathogen causing severe hospital-acquired infections.
• It exhibits significant biofilm formation and antibiotic resistance.
• Multi-drug resistant (MDR) strains pose a growing clinical challenge.

Purpose of the Study:

• To evaluate the efficacy of bacteriophages, antibiotics, and antimicrobial peptides (BAP) against MDR S. marcescens biofilms.
• To determine the synergistic effects of combining these therapeutic agents.
• To establish a potential therapeutic framework for device-associated infections.

Main Methods:

• Utilized an in vitro biofilm model with fourteen MDR S. marcescens isolates.
• Tested bacteriophages, antibiotics (penicillin-streptomycin, kanamycin, ciprofloxacin), and antimicrobial peptides individually and in combination.
• Employed microscopy and viability assays to assess biofilm disruption and bacterial clearance.

Main Results:

• Phage and sub-MIC antibiotic combinations reduced biofilm biomass but did not achieve complete eradication.
• The addition of an antimicrobial peptide cocktail to the phage-antibiotic regimen eradicated 99.99% of planktonic and biofilm MDR S. marcescens.
• Microscopy and viability assays confirmed significant biofilm disruption and bacterial clearance without regrowth.

Conclusions:

• A multifaceted therapeutic approach combining bacteriophages, antibiotics, and antimicrobial peptides is highly effective against MDR S. marcescens.
• Simultaneous interference with bacterial cell wall synthesis, protein translation, DNA replication, and membrane integrity overcomes antimicrobial defenses.
• This strategy presents a promising framework for managing device-associated infections caused by MDR pathogens.