and activity of d-serine in combination with -lactam antibiotics against methicillin-resistant
Acta Pharmaceutica Sinica B
; (6): 496-504, 2019.
Article
in En
| WPRIM
| ID: wpr-774964
Responsible library:
WPRO
ABSTRACT
As d-amino acids play important roles in the physiological metabolism of bacteria, combination of d-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate and activity of d-serine alone and in combination with -lactams against methicillin-resistant (MRSA) strains, and to explore the possible sensitization mechanisms. The activity of d-serine, -lactams alone and in combinations was evaluated both by standard MICs, time-kill curves and checkerboard assays, and by murine systemic infection model as well as neutropenic thigh infection model. An synergistic effect was demonstrated with the combination of d-serine and -lactams against MRSA standard and clinical strains. Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to -lactam alone groups. Initial mechanism study suggested possible revision of d-alanine-d-alanine residue to d-alanine-d-serine in peptidoglycan by adding of d-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, d-serine had synergistic activity in combination with -lactams against MRSA strains both and . Considering the relatively good safety of d-serine alone or in combination with -lactams, d-serine is worth following up as new anti-MRSA infection strategies.
Full text:
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Database:
WPRIM
Language:
En
Journal:
Acta Pharmaceutica Sinica B
Year:
2019
Document type:
Article