D-Serine inhibits the attachment and biofilm formation of methicillin-resistant Staphylococcus aureus
D-Serine inhibits the attachment and biofilm formation of methicillin-resistant Staphylococcus aureus
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DOI：
10.1016/j.bbrc.2020.12.078
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发表时间：
2021-01-22
影响因子：
3.1
通讯作者：
Wada, Takashi
中科院分区：
文献类型：
--
作者：
Iwata, Yasunori;Sakai, Norihiko;Wada, Takashi
前言：虽然临床上已有治疗耐甲氧西林金黄色葡萄球菌(MRSA)的药物，但MRSA感染仍是一种危及生命的疾病。细菌附着和生物膜的形成是引起MRSA感染的重要因素。控制耐甲氧西林金黄色葡萄球菌的附着和生物被膜的形成可能会降低耐甲氧西林金黄色葡萄球菌的感染率。根据最近的数据，一些氨基酸可以减少MRSA在平板上的附着，但其确切的抑制机制尚不清楚。因此，我们在体外和体内MRSA感染模型中探讨了氨基酸对细菌黏附和生物被膜形成的影响。方法：在贴壁实验中检测氨基酸对MRSA和大肠杆菌的抑制作用。结果：在氨基酸中，D-丝氨酸(D-Serine，D-Ser)可降低MRSA在平板上的黏附能力。添加D-Ser不影响MRSA的增殖；因此，D-Ser可能只起到防止附着和生物被膜形成的作用。然后，我们分析了与附着和生物膜形成相关的基因的表达。D-丝氨酸可降低AGRA、SARS、ICAA、DltD和SdrD的表达。此外，经D-丝氨酸处理的聚氯乙烯导管具有较少的MRSA菌落。在导管诱导的腹膜炎模型中，D-丝氨酸治疗也降低了感染的严重程度。结论：D-Ser通过减少相关基因的表达，抑制MRSA的附着和生物被膜的形成。此外，在小鼠模型中，D-丝氨酸的应用可降低导管感染的严重程度。因此，D-丝氨酸可能是治疗耐甲氧西林金黄色葡萄球菌和大肠杆菌感染的一种有前途的选择。(C)2020 Elsevier Inc.保留所有权利。
Introduction: Although therapeutic agents for methicillin-resistant Staphylococcus aureus (MRSA) are clinically available, MRSA infection is still a life-threatening disease. Bacterial attachment and biofilm formation contribute significantly to the initiation of MRSA infection. Controlling MRSA's attachment and biofilm formation might reduce the frequency of MRSA infection. According to recent data, some amino acids can reduce MRSA's attachment on plates; however, their precise inhibitory mechanisms remain unclear. Therefore, we explored the effect of the amino acids on bacterial adhesion and biofilm formation in vitro and in vivo MRSA infection models.Methods: We tested the inhibitory effect of amino acids on MRSA and Escherichia coli (E. coli) in the attachment assay. Moreover, we evaluated the therapeutic potential of amino acids on the in vivo catheter infection model.Results: Among the amino acids, D-Serine (D-Ser) was found to reduce MRSA's ability to attach on plate assay. The proliferation of MRSA was not affected by the addition of D-Ser; thus, D-Ser likely only played a role in preventing attachment and biofilm formation. Then, we analyzed the expression of genes related to attachment and biofilm formation. D-Ser was found to reduce the expressions of AgrA, SarS, IcaA, DltD, and SdrD. Moreover, the polyvinyl chloride catheters treated with D-Ser had fewer MRSA colonies. D-Ser treatment also reduced the severity of infection in the catheter-induced peritonitis model. Moreover, D-Ser reduced the attachment ability of E. coli.Conclusion: D-Ser inhibits the attachment and biofilm formation of MRSA by reducing the expression of the related genes. Also, the administration of D-Ser reduces the severity of catheter infection in the mouse model. Therefore, D-Ser may be a promising therapeutic option for MRSA as well as E. coli infection. (C) 2020 Elsevier Inc. All rights reserved.