Chenodeoxycholic Acid-Amikacin Combination Enhances Eradication of Staphylococcus aureus

Area of Science:

• Microbiology
• Pharmacology
• Traditional Chinese Medicine

Background:

• Antibiotic resistance is a growing global health crisis.
• Novel antibiotic development is lagging, necessitating alternative strategies.
• Traditional Chinese Medicine (TCM) components offer potential for antimicrobial applications.

Purpose of the Study:

• To identify non-antibiotic compounds that can enhance the efficacy of existing antibiotics.
• To investigate the synergistic effects of chenodeoxycholic acid (CDCA) with amikacin against Staphylococcus aureus.
• To explore the potential of TCM derivatives in combating antibiotic-resistant bacterial infections.

Main Methods:

• Screening of antibiotic and non-antibiotic combinations.
• In vitro testing of synergistic activity against Staphylococcus aureus, including methicillin-resistant strains (MRSA), small-colony variants (SCVs), biofilms, and persisters.
• In vivo efficacy evaluation in a mouse infection model.
• Mechanistic studies on CDCA's effect on aminoglycoside uptake and reactive oxygen species (ROS) generation.

Main Results:

• Chenodeoxycholic acid (CDCA) demonstrated synergy with amikacin against Staphylococcus aureus.
• The CDCA-amikacin combination was effective against diverse MRSA variants, including SCVs, biofilms, and persisters.
• CDCA enhanced amikacin efficacy by increasing bacterial uptake via proton motive force dissipation and potentiating ROS generation by inhibiting superoxide dismutase.
• The combination therapy protected a mouse model from S. aureus infections.

Conclusions:

• Chenodeoxycholic acid (CDCA) is a promising agent for enhancing aminoglycoside activity against Gram-positive pathogens like Staphylococcus aureus.
• TCM components, such as CDCA, can be valuable in developing strategies to overcome antibiotic resistance.
• This study supports the repurposing of TCM components to combat multidrug-resistant infections and extend the utility of existing antibiotics.