D-cycloserine increases the effectiveness of vancomycin against vancomycin-highly resistant Staphylococcus aureus
D-cycloserine increases the effectiveness of vancomycin against vancomycin-highly resistant Staphylococcus aureus
复制标题
D-环丝氨酸可提高万古霉素对万古霉素高度耐药金黄色葡萄球菌的有效性
DOI：
10.1038/ja.2017.56
复制
发表时间：
2017
影响因子：
3.3
通讯作者：
Sekimizu Kazuhisa
中科院分区：
文献类型：
--
作者：
Tabuchi Fumiaki;Matsumoto Yasuhiko;Ishii Masaki;Tatsuno Keita;Okazaki Mitsuhiro;Sato Tomoaki;Moriya Kyoji;Sekimizu Kazuhisa
万古霉素是临床上广泛使用的治疗耐甲氧西林金黄色葡萄球菌感染的药物。部分患者对万古霉素治疗反应较弱。我们以前曾报道，β-内酰胺类药物增加了经过反复体外诱变和万古霉素筛选后获得的万古霉素高度耐药金黄色葡萄球菌对万古霉素的敏感性。我们发现，与D-环丝氨酸联合处理后，VRSA菌株对万古霉素的敏感性显著增加。另一方面，VRSA与杆菌素、磷霉素、红霉素、林可霉素、庆大霉素、左氧氟沙星或乳酸链球菌素合用并未显示增加对万古霉素的敏感性。此外，在家蚕体内感染模型中，万古霉素和D-环丝氨酸联合治疗显示出治疗效果，而单独使用两种化合物则没有效果。这些结果表明，万古霉素和D-环丝氨酸联合治疗VRSA引起的感染性疾病可能是有效的。
Vancomycin is a widely used clinical drug to treat for infection by methicillin-resistant Staphylococcus aureus. Some patients show a weak response to vancomycin treatment. We previously reported that β-lactams increase the susceptibility to vancomycin by vancomycin-highly resistant S. aureus (VRSA) strains obtained following repeated in vitro mutagenesis and vancomycin selection. Here we found that the susceptibility of the VRSA strains to vancomycin was remarkably increased by combined treatment with D-cycloserine. On the other hand, VRSA did not show increased susceptibility to vancomycin in combination with bacitracin, fosfomycin, erythromycin, lincomycin, gentamicin, levofloxacin or nisin. Furthermore, in an in vivo infection model with silkworms, combined treatment with vancomycin and D-cycloserine exhibited therapeutic effects, whereas treatment with each compound alone did not. These findings suggest that combined treatment with vancomycin and D-cycloserine could be therapeutically effective against infectious diseases caused by VRSA.