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含色氨酸系列抗菌肽对多药耐药粪肠球菌的抗菌作用 被引量:3

Bactericidal mechanism of tryptophan-containing antimicrobial peptides against multiple-drug resistant Enterococcus faecalis
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摘要 粪肠球菌是院内感染中最常见的一种革兰氏阳性致病菌,与多种疾病密切相关.近年来,由于抗生素的滥用,粪肠球菌对市场上的多种抗生素都有不同程度的抗性,死于粪肠球菌感染的患者人数逐年增加,因此,迫切需要寻找和开发新的抗菌药物.抗菌肽是广泛存在于生物体内的一种小分子肽,具有广谱性、高效性、稳定性等特点,其独特的杀菌机理使细菌不易产生耐药性,因此,抗菌肽是目前最有应用前景的新型抗菌药物.研究了含色氨酸系列抗菌肽对临床分离的多药耐药粪肠球菌的抗菌活性及膜作用机制.结果显示含色氨酸系列抗菌肽对多药耐药粪肠球菌具有高杀菌活性,其作用靶点位于细胞膜上.通过增加多药耐药粪肠球菌外膜和内膜的通透性,并扰乱膜稳定性,使细胞内容物泄漏致细胞死亡.含色氨酸系列抗菌肽还能通过抑制多药耐药粪肠球菌群体感应系统中fsr各组分的表达,抑制毒性因子自溶素和明胶酶的活性,降低生物被膜组分胞外DNA的生成量,最终抑制生物被膜的生成. Enterococcus faecalis is one of the most common gram-positive bacteria in nosocomial infection and is closely related to many diseases.In recent years,with widespread use of antibiotics,E.faecalis has developed resistance to multiple groups of traditional antibiotics,and results in increasing in the number of patients who died of infection caused by E.faecalis.Therefore,it is an urgent for development of new antibiotics against multidrug-resistant bacteria.Antimicrobial peptides(AMPs),as small molecule peptides,exhibit rapid bactericidal activity toward a broad spectrum of gram-negative and-positive bacteria,and are being considered as potential alternatives to current antimicrobial agents,particularly with the emergent problem of drug-resistant pathogenic bacteria.This present study aims to investigate the antimicrobial activity of a series of Trp-containing antimicrobial peptides against multidrug resistant E.faecalis(MREF).The results showed that the Trp-containing antimicrobial peptides displayed high antimicrobial activity against MREF0321,a clinically isolated strain.I4W and L5W targeted on the MREF0321 cell membrane,resulting in bacterial dye through increasing the membrane permeability of MREF0321.Meanwhile,I4W and L5W could inhibit the biofilms formation of MREF0321 by inhibiting the expression of genes related with virulence factors gelatinase and autolysin in the quorum sensing system,and reducing the production of extracellular DNA(eDNA)and extra-polysaccharides of biofilm.
作者 尚德静 赵蕾 王野 姜凤全 SHANG Dejing;ZHAO Lei;WANG Ye;JIANG Fengquan(School of Science, Liaoning Normal University, Dalian 116081, China;Clinical Laboratory, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China)
出处 《辽宁师范大学学报(自然科学版)》 CAS 2021年第3期353-364,共12页 Journal of Liaoning Normal University:Natural Science Edition
基金 国家自然科学基金资助项目(31672289)。
关键词 粪肠球菌 多药耐药 含色氨酸系列抗菌肽 细胞膜 生物被膜 Enterococcus faecalis multiple-drug resistance Trp-containing antimicrobial peptides me-mbrane biofilm
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