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Diverse Effects of Small Molecule Inhibitors on Actin Cytoskeleton Dynamics in HIV-1 Infection 小分子抑制剂对HIV-1感染肌动蛋白细胞骨架动力学的不同影响
Q4 Immunology and Microbiology Pub Date : 2019-06-01 DOI: 10.4167/JBV.2019.49.2.69
Y. Shin, Byeong-Sun Choi, Kyung-Chang Kim, Kisoon Kim, C. Yoon
©This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). The dynamics of the actin cytoskeleton plays a pivotal role in the process of cell division, the transportation of organelles, vesicle trafficking and cell movement. Human immunodeficiency virus type 1 (HIV-1) hijacks the actin dynamics network during the viral entry and migration of the pre-integration complex (PIC) into the nucleus. Actin dynamics linked to HIV-1 has emerged as a potent therapeutic target against HIV infection. Although some inhibitors have been intensely analyzed with regard to HIV-1 infection, their effects are sometimes disputed and the exact mechanisms for actin dynamics in HIV infection have not been well elucidated. In this study, the small molecules regulating HIV-1 infection from diverse inhibitors of the actin dynamic network were screened. Two compounds, including Chaetoglobosin A and CK-548, were observed to specifically bar the viral infection, while the cytochalasin family, 187-1, N-WASP inhibitor, Rho GTPase family inhibitors (EHop-016, CID44216842, and ML-141) and LIMK inhibitor (LIM domain kinase inhibitor) increased the viral infection without cytotoxicity within a range of ~ μM. However, previously known inhibitory compounds of HIV-1 infection, such as Latrunculin A, Jasplakinolide, Wiskostatin and Swinholide A, exhibited either an inhibitory effect on HIV-1 infection combined with severe cytotoxicity or showed no effects. Our data indicate that Chaetoglobosin A and CK-548 have considerable potential for development as new therapeutic drugs for the treatment of HIV infection. In addition, the newly identified roles of Cytochalasins and some inhibitors of Rho GTPase and LIMK may provide fundamental knowledge for understanding the complicated actin dynamic pathway when infected by HIV-1. Remarkably, the newly defined action modes of the inhibitors may be helpful in developing potent anti-HIV drugs that target the actin network, which are required for HIV infection.
©这是一篇根据知识共享署名非商业许可条款分发的开放获取文章(http://creativecommons.org/license/by-nc/3.0/)。肌动蛋白细胞骨架的动力学在细胞分裂、细胞器运输、囊泡运输和细胞运动过程中起着关键作用。人类免疫缺陷病毒1型(HIV-1)在病毒进入和整合前复合体(PIC)迁移到细胞核的过程中劫持肌动蛋白动力学网络。与HIV-1相关的肌动蛋白动力学已成为对抗HIV感染的有效治疗靶点。尽管一些抑制剂已被深入分析与HIV-1感染有关,但它们的作用有时存在争议,并且肌动蛋白动力学在HIV感染中的确切机制尚未得到很好的阐明。在本研究中,从肌动蛋白动态网络的不同抑制剂中筛选出调节HIV-1感染的小分子。观察到两种化合物,包括毛球蛋白A和CK-548,可特异性阻断病毒感染,而细胞松弛素家族187-1、N-WASP抑制剂、Rho GTPase家族抑制剂(EHop-016、CID44216842和ML-141)和LIMK抑制剂(LIM结构域激酶抑制剂)在~μM范围内增加病毒感染,但没有细胞毒性。然而,先前已知的HIV-1感染的抑制性化合物,如Latrunculin A、Jasplakinolde、Wiskostatin和Swinholide A,对HIV-1感染表现出抑制作用并伴有严重的细胞毒性,或者没有表现出任何作用。我们的数据表明,毛球蛋白A和CK-548作为治疗HIV感染的新药物具有相当大的开发潜力。此外,新发现的细胞松弛素和Rho-GTPase和LIMK的一些抑制剂的作用可能为理解HIV-1感染时复杂的肌动蛋白动力学途径提供基础知识。值得注意的是,新定义的抑制剂的作用模式可能有助于开发针对肌动蛋白网络的强效抗HIV药物,而肌动蛋白网络是HIV感染所必需的。
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引用次数: 2
Association Between Toxin-antitoxin Systems on Plasmids and Persister Formation in CTX-15-producing Klebsiella pneumoniae ST11 Isolates 质粒上毒素-抗毒素系统与产生CTX-15的肺炎克雷伯菌ST11分离株持久性形成的关系
Q4 Immunology and Microbiology Pub Date : 2019-06-01 DOI: 10.4167/JBV.2019.49.2.53
Eun Seon Chung, So Yeon Kim, K. Ko
We investigated the effect of toxin-antitoxin (TA) systems in bla CTX-M-15 -bearing plasmids of Klebsiella pneumoniae on persister formation. The persister formation rate was notably high in transconjugants in plasmids bearing TA system than the transconjugants in plasmids bearing no TA systems. Activation of relA and spoT expression was higher in transconjugants with plasmids bearing TA systems. Thus, TA systems in plasmids may contribute to the maintenance of bla CTX-M-15 -bearing plasmids and host survival via persister formation. Plasmids were obtained from four CTX-M-15-producing K. pneumoniae ST11 clinical isolates that were collected from patients in Hong Kong, Malaysia, India, and Thailand (HK02-026, M16-13, IN03-01, and TH02-34, respectively). Their whole plasmid sequences were determined previously (GenBank accession numbers, KY751926, KY751925, KY499796, and KY499797) (14). While TA genes, such as pemIK, mok-hok, and vagCD, were identified on the bla CTX-M-15 -bearing plasmids of HK02-026 and M16-13 (TA+), the bla CTX-M-15 -bearing plasmids of IN03-01 and TH02-34 had no TA genes (TA – ). Then, recovered plasmids were transferred to E. coli J53 cells, as described previously (6). In vitro antimicrobial susceptibility testing was performed by the broth microdilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines (15), and susceptibility was defined according to CLSI breakpoints. E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were used as control strains.
我们研究了携带肺炎克雷伯菌CTX-M-15的bla质粒中毒素-抗毒素(TA)系统对持久性细菌形成的影响。携带TA系统的质粒中的转偶联物中的持续物形成率显著高于不携带TA系统质粒中的跨偶联物。在具有携带TA系统的质粒的转导偶联物中,relA和spoT表达的激活更高。因此,质粒中的TA系统可能有助于维持携带bla CTX-M-15的质粒,并通过持续形成宿主存活。从香港、马来西亚、印度和泰国的患者中收集的四种产生CTX-M-15的肺炎克雷伯菌ST11临床分离株(分别为HK02-026、M16-13、IN03-01和TH02-34)获得质粒。它们的全质粒序列先前已确定(GenBank登录号,KY751926、KY751925、KY499796和KY499797)(14)。虽然在HK02-026和M16-13(TA+)的bla CTX-M-15携带质粒上鉴定了TA基因,如pemIK、mok-hok和vagCD,但IN03-01和TH02-34的bla CTX-M-15携带质粒没有TA基因(TA-)。然后,将回收的质粒转移到大肠杆菌J53细胞中,如前所述(6)。根据临床和实验室标准研究所(CLSI)指南(15),通过肉汤微量稀释法进行体外抗菌药敏试验,并根据CLSI断点定义药敏。使用大肠杆菌ATCC 25922和铜绿假单胞菌ATCC 27853作为对照菌株。
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引用次数: 0
Our Hantaan Virus Became a New Family, Hantaviridae in the Classification of Order Bunyavirales. It will Remain as a History of Virology 我国汉坦病毒在布尼亚病毒目分类中成为汉坦病毒科新科。它将作为病毒学的历史而存在
Q4 Immunology and Microbiology Pub Date : 2019-06-01 DOI: 10.4167/jbv.2019.49.2.45
H. Lee, Jin-Won Song
the order Bunyavirales, previously family Bunyaviridae, was by new order of families including Hantaviridae family, now the on of Hantaviridae is now a family of the order Bunyavirales, and the prototype virus species is Hantaan orthohantavirus. The family Hantaviridae is divided into four subfamilies including Mammantavirinae, Repantavirinae, Actantavirinae and Agantavirinae. The subfamily Mammantavirinae is divided into four genera including Orthohantavirus, Loanvirus, Mobatvirus and Thottimvirus. The four Hantavirus species have been found in Korea including three Orthohantaviruses (Hantaan orthohantavirus, Seoul orthohantavirus and Jeju orthohantavirus) and one Thottimvirus (Imjin thottimvirus).
布尼亚病毒目,以前的布尼亚病毒科,是由包括汉坦病毒科在内的新目组成的,现在汉坦病毒科的分支现在是布尼亚病毒目的一个科,原型病毒物种是汉坦正汉坦病毒。汉坦病毒科分为四个亚科,包括mammantaavirinae, Repantavirinae, Actantavirinae和Agantavirinae。Mammantavirinae亚科分为四个属,包括Orthohantavirus, Loanvirus, Mobatvirus和Thottimvirus。目前,在国内发现了3种(韩滩病毒、首尔病毒、济州病毒)和1种(林津病毒)等4种病毒。
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引用次数: 1
Epidemiology ofLegionellaand Climatic Variables in Seoul, Korea 韩国首尔军团菌流行病学与气候变量
Q4 Immunology and Microbiology Pub Date : 2019-06-01 DOI: 10.4167/jbv.2019.49.2.59
Sang-Hun Park, Young-Hee Jin, Mi-Jin Ahn, Sunghee Han, H. Kim, Jin Seok Kim, Joo-Hyun Park, Chae-Kyu Hong, Sook Park, Ah-Ryung Oh, Jibho Lee, Il-Young Kim, Yong-Seoung Shin
Legionella species are abundant in the built environment and are increasingly recognized as a cause of Legionnaires ’ disease (LD). As the number of cases of Legionnaires ’ disease acquired by local communities in the Seoul metropolitan area in Korea has been increased, there was concern that changes in environmental factors could affect disease outbreaks. We described the association between climatic variables and occurrence of legionellosis in Korea and Legionella detection rate in Seoul area. A total of 418 cases of legionellosis were reported between 2014 and 2017. There was a seasonal peak in summer. LD continuously occurred from early spring to winter every year and rapidly increased in summer. In the regression analysis, the primary variables of interest- PM2.5 (  g/m 3 ), NO 2 (ppb), and a number of the date of issue O 3 warning were not significant except for average temperature (R 2 =0.8075). The Legionella detection rate in Seoul, Korea showed a trend similar to precipitation (P=0.708, ANOVA). A relatively high proportion of Legionella detection rate was shown, especially cooling tower (17.7%) and public bath (19.3%). This finding is in line with current understanding of the ecological profile of this pathogen and supports the assertion that legionellosis occurs through contamination of water
军团菌在建筑环境中数量丰富,越来越多地被认为是军团病(LD)的病因。随着韩国首尔都会区当地社区感染军团病的病例数量增加,人们担心环境因素的变化可能会影响疾病的爆发。我们描述了气候变量与韩国军团菌病发生率和首尔地区军团菌检测率之间的关系。2014年至2017年间,共报告418例军团菌病病例。夏天有一个季节性的高峰。LD从每年早春到冬季持续发生,夏季迅速增加。在回归分析中,感兴趣的主要变量PM2.5( g/m3)、NO 2(ppb)和发布O3预警的日期数除平均温度外均不显著(R2=0.8075)。韩国首尔的军团菌检测率显示出与降水相似的趋势(P=0.708,ANOVA)。军团菌的检出率相对较高,尤其是冷却塔(17.7%)和公共浴池(19.3%)。这一发现符合目前对该病原体生态特征的理解,并支持军团菌病是通过水污染发生的说法
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引用次数: 3
Delafloxacin, a New Miracle in Antibiotics Armamentarium for Bacterial Infections 德拉沙星:抗菌药库中治疗细菌感染的新奇迹
Q4 Immunology and Microbiology Pub Date : 2019-03-01 DOI: 10.4167/JBV.2019.49.1.39
M. S. Rahman, Y. Koh
©This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). The persistent antibiotics resistant issue has emerged as an influencing factor to deteriorate community health. So, new antibiotics development is urgent for the treatment of bacterial infections. Alternatively, delafloxacin is an eminent new fluoroquinolone, and chemically distinct from older fluoroquinolones. There is lack of proton substituent that indicates the poor acidic property of the drug. It also has a good intracellular penetration capacity that increases the intensity of the bactericidal property in acidic environment. Delafloxacin is a super active drug against the skin and soft tissue infections (SSTIs) and community-acquired respiratory tract infections. Delafloxacin also exhibits better efficacy against pathogens which are resistant to other fluoroquinolones, such as methicillin-resistant Staphylococcus aureus (MRSA). Delafloxacin received approval from the US Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSI). Phase III clinical trial among patients with community-acquired pneumonia (CAP) is ongoing to evaluate the effectiveness of delafloxacin. From the aforementioned arguments, delafloxacin will be a prominent candidate for the upcoming antibacterial agent. Similarly, delafloxacin can be a crucial drug to fight against ABSSI.
©这是一篇根据知识共享署名非商业许可条款分发的开放获取文章(http://creativecommons.org/license/bync/3.0/)。持续的抗生素耐药性问题已成为恶化社区健康的一个影响因素。因此,开发新的抗生素是治疗细菌感染的迫切需要。或者,德拉沙星是一种杰出的新型氟喹诺酮类药物,在化学上与旧的氟喹诺酮药物不同。缺乏质子取代基表明该药物的酸性较差。它还具有良好的细胞内渗透能力,在酸性环境中提高了杀菌性能的强度。Dela氟沙星是一种抗皮肤和软组织感染(SSTI)以及社区获得性呼吸道感染的超活性药物。德拉氟沙星对其他氟喹诺酮类药物具有耐药性的病原体也表现出更好的疗效,如耐甲氧西林金黄色葡萄球菌(MRSA)。特拉沙星获得了美国食品药品监督管理局(FDA)的批准,用于治疗急性细菌性皮肤和皮肤结构感染(ABSSI)。社区获得性肺炎(CAP)患者的III期临床试验正在进行中,以评估德拉沙星的有效性。从上述论点来看,德拉沙星将是即将推出的抗菌剂的突出候选药物。同样,德拉沙星也是对抗ABSSI的关键药物。
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引用次数: 2
RND efflux pump systems inAcinetobacter, with special emphasis on their role in quorum sensing 不动杆菌RND外排泵系统,特别强调其在群体感应中的作用
Q4 Immunology and Microbiology Pub Date : 2019-03-01 DOI: 10.4167/JBV.2019.49.1.1
Bindu Subhadra, M. Oh, Chul Hee Choi
©This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). Acinetobacter is an important opportunistic, multidrug resistant pathogen causing majority of nosocomial infections worldwide. The multidrug resistance is attributed by a plethora of efflux pumps and the overexpression of the same mediates export of antimicrobial agents. Quorum sensing (QS) is the cell-to-cell communication system in which bacteria produces specific signaling molecules which are transported out to the surrounding environment to communicate with other bacterial cells. It has been noticed that multidrug efflux pumps like resistance-nodulation-cell division (RND) efflux pumps play an important role in QS by exporting these signaling molecules. This review discusses various RND efflux pumps and the current understanding of the interrelationship of RND efflux pumps and QS in Acinetobacter spp. Studies demonstrate that RND efflux pumps could be considered as potential targets to block QS thereby reducing pathogenesis and antibiotic resistance. The known RND efflux pump-mediated quorum quenching strategies for Acinetobacter and other bacterial strains are discussed in detail. Finally, the prospective quorum quenching strategies targeting the transcriptional regulators of RND efflux pumps to inhibit multidrug efflux pumps are addressed.
©这是一篇根据知识共享署名非商业许可条款分发的开放获取文章(http://creativecommons.org/许可证/通过nc/3.0/)。不动杆菌是一种重要的机会性、多药耐药性病原体,导致全球大多数医院感染。多药耐药性是由过多的外排泵引起的,而过多的内排泵介导了抗微生物剂的输出。群体感应(QS)是一种细胞间通信系统,在该系统中,细菌产生特定的信号分子,这些信号分子被输送到周围环境中,与其他细菌细胞进行通信。已经注意到,多药外排泵,如耐药结节细胞分裂(RND)外排泵通过输出这些信号分子在QS中发挥重要作用。这篇综述讨论了各种RND外排泵以及目前对不动杆菌中RND外排出泵和QS相互关系的理解。研究表明,RND外流出泵可以被认为是阻断QS的潜在靶点,从而降低发病机制和抗生素耐药性。详细讨论了已知的RND外排泵介导的不动杆菌和其他菌株的群体猝灭策略。最后,针对RND外排泵的转录调节因子抑制多药外排泵,提出了前瞻性的群体猝灭策略。
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引用次数: 7
Apolipoprotein E Genotype and Expression Correlated with Hepatitis C Virus Genotype and Infection 载脂蛋白E基因型及其表达与丙型肝炎病毒基因型和感染的相关性
Q4 Immunology and Microbiology Pub Date : 2019-03-01 DOI: 10.4167/JBV.2019.49.1.27
G. Park, H. Jo, Hye-Ran Kim, Min-Ju Kim, K. Shin, S. Hong, Kyung-Soo Chang
©This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. Several studies reported that HCV particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. However, the relationship between apoE gene polymorphisms and HCV genotypes in patients with HCV is less well understood. The aim of this study was to investigate the association between apoE gene polymorphism and HCV genotypes in patients. The HCV genotypes were identified among the 124 patients infected with HCV, and the genetic characteristics of the HCV genotype were analyzed. In addition, the results of the clinical laboratory test were comparatively analyzed according to the classified genotypes. Both HCV 1b (n=80) and 2a (n=42) patients had higher AFP, AST, ALT, ALP, γ-GTP, apoB, and apoE values compared with the normal control group. In particular, apoB and apoE levels were statistically significantly higher in the HCV 2a patients (P<0.05) and apoE levels were significantly higher in the HCV 1b patients (P<0.000). According to the results the patients with HCV genotype 1b showed higher values of liver damage related indicators and apoB expression than the patients with HCV genotype 2a. The fat related indicators and apoE expression were not different between the two major HCV genotypes (2a and 1b). We anticipate that the apoE ε3 allele is the most common type in HCV genotype 1b (89.2%) and 2a (91.7%). As a result of apoE genotyping, we confirmed an association with HCV infection and the apoE ε3 allele. However, the ratios of the apoE ε3 allele among the patients with genotype 1b and 2a were similar to each other.
©这是一篇根据知识共享署名非商业许可条款分发的开放获取文章(http://creativecommons.org/丙型肝炎病毒(HCV)是一种全球流行的人类病原体,在大多数感染者中会导致持续的肝脏感染。几项研究报道,丙型肝炎病毒颗粒富含载脂蛋白E(apoE),apoE是丙型肝炎病毒感染和产生所必需的。然而,丙型肝炎患者apoE基因多态性与丙型肝炎病毒基因型之间的关系尚不清楚。本研究的目的是探讨载脂蛋白E基因多态性与患者丙型肝炎病毒基因型之间的关系。对124例丙型肝炎病毒感染者进行了基因型鉴定,并对其基因型的遗传特征进行了分析。此外,根据分类的基因型对临床实验室测试结果进行了比较分析。与正常对照组相比,HCV 1b(n=80)和2a(n=42)患者的AFP、AST、ALT、ALP、γ-GTP、apoB和apoE值均较高。特别是载脂蛋白B和载脂蛋白E水平在HCV 2a型患者中显著升高(P<0.05),载脂蛋白e水平在HCV 1b型患者中明显升高(P>0.000)。两种主要HCV基因型(2a和1b)之间的脂肪相关指标和apoE表达没有差异。我们预计载脂蛋白Eε3等位基因是HCV基因型1b(89.2%)和2a(91.7%)中最常见的类型。然而,基因型为1b和2a的患者中apoEε3等位基因的比例彼此相似。
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引用次数: 0
Effector Pathways of Toll-like Receptor-inducible Innate Immune Responses in Macrophages 巨噬细胞中Toll样受体诱导的先天免疫反应的效应通路
Q4 Immunology and Microbiology Pub Date : 2019-03-01 DOI: 10.4167/JBV.2019.49.1.12
E. Jo, Hyun-Woo Suh, J. Park
©This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). Toll-like receptors (TLR) are well-characterized pattern recognition receptors that can recognize and respond to diverse pathogen-associated or danger-associated molecular patterns during infection. TLR signaling in macrophages triggers in the intracellular signaling pathways through the recruitment of various adaptor and signaling proteins, and results in the activation of effector mechanisms and pathways that are important for host defense to intracellular bacteria. Effector mechanisms include inflammatory responses, cytokine generation, production of reactive oxygen species, and antimicrobial proteins. Accumulating studies showed that autophagy is a key pathway in the maintenance of homeostasis and housekeeping functions during infection and inflammation. In this review, we summarize the major effector pathways and mechanisms in the activation of TLR-inducible innate immune responses in macrophages. In addition, we focus the emerging evidence of crosstalk between autophagy and TLR-mediated signaling in terms of effector function of innate immune responses. A better understanding of effector functions by the activation of TLR-mediated signaling cascades contributes to the development of new therapeutics and vaccines against various intracellular pathogenic infections.
©这是一篇根据知识共享署名非商业许可条款分发的开放获取文章(http://creativecommons.org/Toll样受体(TLR)是一种特征良好的模式识别受体,可以在感染期间识别和响应各种病原体相关或危险相关的分子模式。巨噬细胞中的TLR信号通过募集各种衔接蛋白和信号蛋白在细胞内信号通路中触发,并导致对宿主防御细胞内细菌很重要的效应机制和通路的激活。效应机制包括炎症反应、细胞因子的产生、活性氧的产生和抗微生物蛋白。越来越多的研究表明,自噬是感染和炎症期间维持体内平衡和内务管理功能的关键途径。在这篇综述中,我们总结了巨噬细胞激活TLR诱导的先天免疫反应的主要效应途径和机制。此外,我们还关注了自噬和TLR介导的信号传导在先天免疫反应的效应器功能方面相互作用的新证据。通过激活TLR介导的信号级联对效应器功能的更好理解有助于开发针对各种细胞内致病性感染的新疗法和疫苗。
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引用次数: 3
Diversity of Genetic Environment ofblaCTX-MGenes and Antimicrobial Susceptibility in Extended-spectrum β-lactamase producingEscherichia coliIsolated in Korea 韩国产β-内酰胺酶大肠埃希菌blactx - m基因遗传环境多样性及药敏研究
Q4 Immunology and Microbiology Pub Date : 2019-01-01 DOI: 10.4167/jbv.2019.49.3.95
Yun-Yi Yang, M. Suh
©This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). Increasing resistance due to the production of extended-spectrum β-lactamase (ESBL) in Escherichia coli is a major problem to public health and CTX-M enzymes have become the most prevalent ESBL worldwide. In this study, resistance profiles of E. coli isolated in Korea and the genetic environments of blaCTX-M genes were analyzed by PCR and direct sequencing to clarify the mechanisms of spread of CTX-M. Resistance rates of CTX-M-producing E. coli, including β-lactams, fluoroquinolones and aminoglycosides, were significantly higher than that of CTX-M-non-producers (p<0.01). Of 41 tested, 39 (95.1%) isolates of CTX-M-producing E. coli showed resistance transfer by conjugation. All the transconjugants harboured large plasmids of 118~172 megadalton. Insertion sequence ISEcp1B was detected in the upstream of the blaCTX-M in 38 (92.7%) isolates with blaCTX-M. ISEcp1B was disrupted by IS26 in 16 (39.0%) isolates with blaCTX-M. ISEcp1B carried -35 and -10 promoter components between right inverted repeat (IRR) and the start codon of blaCTX-M. orf477 or IS903D was observed in the downstream of the blaCTX-M in all the isolates with blaCTX-M-3/15/55 or with blaCTX-M-14/27, respectively. Sequence similar to IRR of ISEcp1B was located downstream of orf477. Target duplication sequences were detected both upstream of IRL and downstream of IRR. These results showed the involvement of ISEcp1B in the mobilization of the resistance genes. In conclusion, the surrounding DNAs of blaCTX-M genes were very diverse, and the spread and the expression of CTX-M may be deeply related with ISEcp1B. These informations will provide important knowledge to control the increase in CTX-M-ESBLs.
©这是一篇基于知识共享署名非商业许可协议(http://creativecommons.org/ License /by-nc/3.0/)的开放获取文章。大肠杆菌产生的广谱β-内酰胺酶(ESBL)引起的耐药性增加是公共卫生面临的主要问题,CTX-M酶已成为全球最普遍的ESBL。本研究对韩国分离的大肠杆菌耐药谱和blaCTX-M基因的遗传环境进行了PCR和直接测序分析,以阐明CTX-M的传播机制。产生ctx - m的大肠杆菌对β-内酰胺类、氟喹诺酮类和氨基糖苷类的耐药率显著高于不产生ctx - m的大肠杆菌(p<0.01)。在所检测的41株菌株中,39株(95.1%)产生ctx - m的大肠杆菌通过偶联产生耐药性转移。所有的转共轭子都含有118~172兆道尔顿的大质粒。在38株(92.7%)blaCTX-M分离株中,在blaCTX-M上游检测到插入序列ISEcp1B。在16株(39.0%)blaCTX-M分离株中,ISEcp1B被IS26破坏。ISEcp1B在blaCTX-M的右反向重复序列(IRR)和起始密码子之间携带-35和-10个启动子成分。在携带blaCTX-M-3/15/55和携带blaCTX-M-14/27的分离株中,在blaCTX-M下游分别观察到orf477和IS903D。与ISEcp1B的IRR相似的序列位于orf477的下游。在IRL的上游和下游均检测到目标重复序列。这些结果表明ISEcp1B参与了抗性基因的动员。综上所述,blaCTX-M基因的周围dna非常多样化,CTX-M的传播和表达可能与ISEcp1B有很深的关系。这些信息将为控制CTX-M-ESBLs的增加提供重要的知识。
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引用次数: 1
Proteome Analysis of Alkylhydroxide Peroxidase-Deficient Isogenic Mutant ofHelicobacter pylori26695 幽门螺杆菌26695烷基氢氧化酶缺陷等基因突变体的蛋白质组学分析
Q4 Immunology and Microbiology Pub Date : 2019-01-01 DOI: 10.4167/jbv.2019.49.4.191
Woo-Kon Lee, B. Chul, M. Shin, Myunghwan Jung, Jin-Sik Park, Jong-Hoon Ha, Dong-Hae Lee, Min Jeong Kim, Jeong-Ih Shin, KangHyung Lyun
©This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). In order to investigate the antioxidant effect of alkylhydroxide peroxidase (ahpC) of Helicobacter pylori (H. pylori) 26695, an ahpC-deficient mutant (H. pylori 26695 ahpC::cat) was generated. ahpC-deficient mutant was grown slowly at lower pressure of oxygen (5% oxygen) compared to the H. pylori 26695. Whole cell proteins isolated form H. pylori 26695 and H. pylori 26695 ahpC::cat were analyzed by MALDI-TOF and tandem-MS. The expression of 15 proteins, including Ppa, HypB, GrpE, Elp, RecA, GroES, Mda66, RibE, NapA, GlnA, BioB, TrxB, Tsf, FumC and Icd, was more than doubled in H. pylori 26695 ahpC::cat. Production of 10 proteins such as UreG, FabE, Adk, Pnp, OorC, AtpA, AtpD, Nqq3, Pfr, and TagD decreased below 50% in H. pylori 26695 ahpC::cat compared to the H. pylori 26695. In microarray analysis, 9 genes including sul1, amiE, frxA, fecA, hyuA, and katA increased in transcription level in H. pylori 26695 ahpC::cat compared to H. pylori 26695. A total of 24 genes, including flaB, protein kinase C inhibitor, cag16, pabC, and sabA, reduced in transcription. 27 genes, including HP0889, showed common expression changes in ahpC, katA, and sodB-deficient mutations. As a result of this study, there were not many genes whose expression was commonly changed by the deletion of each of the three major antioxidant enzymes of H. pylori. These results showed the functions and regulation of the three antioxidant enzymes were different in H. pylori.
©这是一篇基于知识共享署名非商业许可协议(http://creativecommons.org/ License /by-nc/3.0/)的开放获取文章。为了研究幽门螺杆菌(h.p ylori) 26695的烷基氢氧化酶(ahpC)的抗氧化作用,制备了ahpC缺陷突变体(h.p ylori 26695 ahpC::cat)。与幽门螺杆菌26695相比,ahpc缺陷突变体在较低的氧气压力(5%氧气)下生长缓慢。采用MALDI-TOF和串联质谱对H. pylori 26695和H. pylori 26695 ahpC::cat分离的全细胞蛋白进行分析。Ppa、HypB、GrpE、Elp、RecA、GroES、Mda66、RibE、NapA、GlnA、BioB、TrxB、Tsf、FumC、Icd等15种蛋白在H. pylori 26695 ahpC::cat中的表达量增加了一倍以上。与H. pylori 26695相比,H. pylori 26695 ahpC::cat中UreG、FabE、Adk、Pnp、OorC、AtpA、AtpD、Nqq3、Pfr和TagD等10种蛋白的产量下降了50%以下。微阵列分析显示,与H. pylori 26695相比,ahpC::cat中sul1、amiE、frxA、fecA、hyuA和katA等9个基因的转录水平升高。共有24个基因,包括flaB、蛋白激酶C抑制剂、cag16、pabC和sabA转录减少。包括HP0889在内的27个基因在ahpC、katA和sodb缺陷突变中表现出共同的表达变化。本研究结果表明,由于幽门螺杆菌三种主要抗氧化酶的缺失而导致表达普遍改变的基因并不多。结果表明,三种抗氧化酶在幽门螺杆菌中的作用和调控是不同的。
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引用次数: 0
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Journal of Bacteriology and Virology
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