本文選題：抗菌肽　切入點(diǎn)：Cbf--　出處：《中國(guó)藥科大學(xué)學(xué)報(bào)》2017年04期

【摘要】：本研究主要探討了新型多肽突變體Cbf-14-2對(duì)攜帶NDM-1基因重組菌(E.coli BL21(DE3)-NDM-1)的抗菌活性及機(jī)制。實(shí)驗(yàn)采用肉湯倍比稀釋活菌計(jì)數(shù)法測(cè)定多肽對(duì)E.coli BL21(DE3)-NDM-1重組菌的MIC/MBC和殺菌曲線,評(píng)價(jià)多肽的體外抗菌活性;采用重組菌腹腔感染法建立小鼠敗血癥模型,評(píng)價(jià)多肽的體內(nèi)抗菌活性;通過Zeta電位分析和流式細(xì)胞術(shù)探討Cbf-14-2抗耐藥細(xì)菌感染的作用機(jī)制。結(jié)果表明,多肽Cbf-14-2對(duì)攜帶NDM-1基因的耐藥細(xì)菌具有良好的抗菌活性(MIC=16μg/m L),能在2 h內(nèi)快速殺滅細(xì)菌;同時(shí),多肽能顯著降低感染小鼠肝、脾、肺和腎臟等組織的細(xì)菌負(fù)載量,對(duì)細(xì)菌顯示出強(qiáng)效清除能力,將小鼠存活率由10%提高至70%。這主要由于Cbf-14-2能與細(xì)菌細(xì)胞膜表面負(fù)電荷發(fā)生靜電結(jié)合,增加對(duì)膜的穿透能力。因此,Cbf-14-2有望成為治療NDM-1耐藥細(xì)菌誘發(fā)感染的潛在抗菌劑。
[Abstract]:In this study, the antimicrobial activity and mechanism of a new polypeptide mutant Cbf-14-2 against E. coli BL21DE3- NDM-1 was studied.The MIC/MBC and bactericidal curves of polypeptides against E.coli BL21(DE3)-NDM-1 recombinant bacteria were determined by broth doubling dilution method, and the in vitro antibacterial activity of polypeptides was evaluated, and the septicemia model of mice was established by the method of intraperitoneal infection of recombinant bacteria to evaluate the antibacterial activity of polypeptides in vivo.Zeta potential analysis and flow cytometry were used to investigate the mechanism of Cbf-14-2 in resistance to bacterial infection.The results showed that polypeptide Cbf-14-2 had good antibacterial activity against drug-resistant bacteria carrying NDM-1 gene, and could kill bacteria quickly within 2 hours, and the amount of bacterial load in liver, spleen, lung and kidney of infected mice was significantly decreased.It showed strong scavenging ability to bacteria and increased the survival rate of mice from 10% to 70%.This is mainly due to the electrostatic binding of Cbf-14-2 to the negative charge on the surface of the bacterial cell membrane, which increases the penetration ability of the membrane.Therefore, Cbf-14-2 is expected to be a potential antimicrobial agent for the treatment of NDM-1-resistant bacteria-induced infections.
【作者單位】： 中國(guó)藥科大學(xué)微生物學(xué)教研室;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(No.81673483) 中央高�；究蒲袠I(yè)務(wù)費(fèi)專項(xiàng)資金資助(No.2632017PT03) 江蘇高校優(yōu)勢(shì)學(xué)科建設(shè)工程資助項(xiàng)目(PADA)~~
【分類號(hào)】：R96

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本文編號(hào)：1724219