Amikacin and bacteriophage treatment modulates outer membrane proteins composition in Proteus mirabilis biofilm

Area of Science:

• Microbiology
• Bacterial Outer Membrane Proteins
• Antimicrobial Resistance

Background:

• Gram-negative bacteria, like Proteus mirabilis, utilize outer membrane proteins (OMPs) as a primary defense against antimicrobials.
• Understanding OMP modifications is crucial for developing effective treatments against antibiotic and bacteriophage resistance.

Purpose of the Study:

• To investigate the role of Proteus mirabilis OMPs in resistance to amikacin and bacteriophages.
• To compare protein expression profiles in wild-type and resistant P. mirabilis variants.

Main Methods:

• Proteomic analysis comparing wild-type P. mirabilis with amikacin-resistant (AMKrsv), phage-resistant (Brsv), and combined amikacin/phage-resistant (AMK/Brsv) variants.
• Identification and quantification of overexpressed and downregulated proteins in resistant strains.

Main Results:

• Resistant variants exhibited significant changes in OMP profiles, with 14, 1, and 5 overexpressed proteins and 13, 5, and 1 downregulated proteins in AMKrsv, Brsv, and AMK/Brsv strains, respectively.
• Combined amikacin-phage treatment resulted in fewer protein alterations compared to single-agent treatments.
• Identified proteins in resistant strains are involved in protein biosynthesis, transcription, signal transduction, and biofilm formation, including elongation factor Tu, NusA, and polyphosphate kinase.

Conclusions:

• OMP modifications in Proteus mirabilis are key to amikacin and phage resistance.
• The combined therapeutic approach of amikacin and phages induces fewer proteomic changes, indicating a potentially more targeted resistance mechanism.
• The identified proteins offer potential targets for developing novel antibiofilm therapies against P. mirabilis.