It takes two to tango: Preserving daptomycin efficacy against daptomycin-resistant MRSA using daptomycin-phage...

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Daptomycin (DAP) is crucial for treating multidrug-resistant Staphylococcus aureus (MRSA).
• Emerging DAP resistance necessitates novel therapeutic strategies.
• Bacteriophage therapy offers a promising approach to combat antibiotic resistance.

Purpose of the Study:

• To investigate the relationship between DAP resistance and sensitivity to bacteriophage Sb-1 in MRSA.
• To evaluate the synergistic potential of phage-antibiotic combinations (PACs) in DAP-resistant strains.
• To explore the impact of DAP monotherapy and DAP-phage treatment on MRSA cell wall morphology.

Main Methods:

• Analysis of 14 clinical MRSA strains, including isogenic DAP-susceptible and DAP-resistant pairs.
• Measurement of bacteriophage efficiency of plating (EOP) and plaque sizes.
• Phage-antibiotic combination (PAC) checkerboard assays.
• Transmission electron microscopy (TEM) of MRSA cell walls.

Main Results:

• DAP-resistant MRSA strains exhibited significantly increased sensitivity to phage Sb-1 (higher EOP and plaque sizes).
• PAC checkerboards showed reduced antagonism in DAP-resistant mutants compared to susceptible strains.
• TEM revealed significantly thicker cell walls in DAP-susceptible strains under DAP monotherapy.

Conclusions:

• Increased sensitivity to bacteriophage Sb-1 accompanies the emergence of DAP resistance in MRSA.
• Phage-antibiotic combinations demonstrate potential for synergistic activity against DAP-resistant MRSA.
• This strategy may help preserve the efficacy of existing antibiotics against challenging infections.