and activity of d-serine in combination with -lactam antibiotics against methicillin-resistant .

Qing WANG; Yuemeng LV; Jing PANG; Xue LI; Xi LU; Xiukun WANG; Xinxin HU; Tongying NIE; Xinyi YANG; Yan Q XIONG; Jiandong JIANG; Congran LI; Xuefu YOU

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and activity of d-serine in combination with -lactam antibiotics against methicillin-resistant .

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

1. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
2. Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
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.