Overcoming Multidrug-Resistant MRSA Using Conventional Aminoglycoside Antibiotics

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Infectious Diseases

Background:

• Multidrug-resistant (MDR) bacteria pose a significant global health threat.
• Antibiotic resistance necessitates novel strategies to resensitize bacteria to existing drugs.

Purpose of the Study:

• To investigate low-temperature photothermal treatment (PTT) using red phosphorus nanoparticles to resensitize methicillin-resistant Staphylococcus aureus (MRSA) to aminoglycoside antibiotics.

Main Methods:

• Proteomic techniques and molecular dynamics (MD) simulations were employed to elucidate the antibacterial mechanism.
• Adenosine triphosphate (ATP) consumption was monitored to assess enzyme inhibition.
• MD simulations analyzed the thermal stability of key enzyme residues.

Main Results:

• Low-temperature PTT selectively potentiated aminoglycoside antibiotics against MRSA.
• The catalytic activity of 2-aminoglycoside phosphotransferase (APH(2″)) was significantly inhibited.
• MD simulations revealed thermal instability in the APH(2″) active site, hindering its catalytic function.

Conclusions:

• Low-temperature PTT combined with aminoglycoside antibiotics effectively resensitizes MRSA.
• This strategy acts as an exogenous-modifying enzyme inhibitor, showing potential for treating MDR bacterial infections.
• The combined therapy demonstrated biocompatibility and efficacy in vivo.