Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter baumannii.

Area of Science:

• Microbiology
• Biotechnology
• Antimicrobial Research

Background:

• Bacteriophage depolymerases degrade bacterial surface polysaccharides (CPS, LPS, EPS).
• These enzymes are explored as antivirulence agents against multidrug-resistant (MDR) bacteria.
• Depolymerases can disarm bacterial capsules, potentially boosting antibiotic efficacy.

Purpose of the Study:

• To identify, clone, and express a depolymerase (Dpo71) from a bacteriophage targeting *Acinetobacter baumannii*.
• To evaluate Dpo71's potential as an antivirulence agent and antibiotic adjuvant.
• To investigate the mechanisms underlying Dpo71's synergistic effects with antibiotics.

Main Methods:

• Cloning and expression of depolymerase Dpo71 in *Escherichia coli*.
• Assessing Dpo71's ability to sensitize MDR *A. baumannii* to human serum and colistin.
• Investigating Dpo71's impact on bacterial outer membrane destabilization and biofilm formation.
• Evaluating Dpo71 efficacy in a *Galleria mellonella* infection model.

Main Results:

• Dpo71 sensitized MDR *A. baumannii* to serum and colistin, with 10 μg/ml Dpo71 achieving complete eradication with 50% serum.
• Dpo71 enhanced colistin's bactericidal effect by improving outer membrane destabilization and bacterial binding.
• Dpo71 inhibited biofilm formation, disrupted pre-formed biofilms, and improved colistin's antibiofilm activity.
• Dpo71 treatment improved survival rates in *Galleria mellonella* models.

Conclusions:

• Recombinant depolymerase Dpo71 acts as an effective antibiotic adjuvant against *Acinetobacter baumannii*.
• Dpo71 enhances antibiotic action by destabilizing the bacterial outer membrane and inhibiting biofilms.
• Dpo71 demonstrates strain-specificity, targeting phage-sensitive *A. baumannii* strains.
• Depolymerases represent a feasible strategy for developing new antibacterials and combating MDR pathogens.