- Author:
Qing WANG
1
;
Yuemeng LV
1
;
Jing PANG
1
;
Xue LI
1
;
Xi LU
1
;
Xiukun WANG
1
;
Xinxin HU
1
;
Tongying NIE
1
;
Xinyi YANG
1
;
Yan Q XIONG
2
;
Jiandong JIANG
1
;
Congran LI
1
;
Xuefu YOU
1
Author Information
- Publication Type:Journal Article
- Keywords: Combination; MRSA; Synergistic effect; d-Serine; β-Lactams
- From: Acta Pharmaceutica Sinica B 2019;9(3):496-504
- CountryChina
- Language:English
- 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.