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Bacteriophages for managing Shigella in various clinical and non-clinical settings. 在各种临床和非临床环境中用于控制志贺氏菌的噬菌体。
Pub Date : 2013-01-01 Epub Date: 2013-05-21 DOI: 10.4161/bact.25098
Lawrence D Goodridge

The control of shigellosis in humans enjoys a prominent position in the history of bacteriophage therapy. d'Herelle first demonstrated the efficacy of phage therapy by curing 4 patients of shigellosis, and several subsequent studies confirmed the ability of phages to reduce Shigella based infection. Shigella spp continue to cause millions of illnesses and deaths each year and the use of phages to control the disease in humans and the spread of the bacteria within food and water could point the way forward to the effective management of an infectious disease with global influence.

人类志贺氏菌病的控制在噬菌体治疗史上占有重要地位。d'Herelle首先通过治愈4例志贺氏菌病患者证明了噬菌体治疗的有效性,随后的几项研究证实了噬菌体减少志贺氏菌感染的能力。志贺氏菌每年继续造成数百万人患病和死亡,利用噬菌体控制人类患病和细菌在食物和水中的传播,可能为有效管理具有全球影响的传染病指明方向。
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引用次数: 24
Biochemical insights into the function of phage G1 gp67 in Staphylococcus aureus. 金黄色葡萄球菌噬菌体G1 gp67功能的生化分析。
Pub Date : 2013-01-01 DOI: 10.4161/bact.24767
Joseph Osmundson, Seth A Darst
Bacteriophage (phage) are among the most diverse and abundant life forms on Earth. Studies have recently used phage diversity to identify novel antimicrobial peptides and proteins. We showed that one such phage protein, Staphylococcus aureus (Sau) phage G1 gp67, inhibits cell growth in Sau by an unusual mechanism. Gp67 binds to the host RNA polymerase (RNAP) through an interaction with the promoter specificity σ subunit, but unlike many other σ-binding phage proteins, gp67 does not disrupt transcription at most promoters. Rather, gp67 prevents binding of another RNAP domain, the α-C-terminal domain, to upstream A/T-rich elements required for robust transcription at rRNA promoters. Here, we discuss additional biochemical insights on gp67, how phage promoters escape the inhibitory function of gp67, and methodological advancements that were foundational to our work.
噬菌体(噬菌体)是地球上最多样化和丰富的生命形式之一。最近的研究利用噬菌体多样性来鉴定新的抗菌肽和蛋白质。我们发现一种这样的噬菌体蛋白,金黄色葡萄球菌(Sau)噬菌体G1 gp67,通过一种不寻常的机制抑制Sau中的细胞生长。Gp67通过与启动子特异性σ亚基的相互作用与宿主RNA聚合酶(RNAP)结合,但与许多其他σ结合噬菌体蛋白不同,Gp67不会破坏大多数启动子的转录。相反,gp67阻止另一个RNAP结构域α- c末端结构域与上游富含A/ t的元件的结合,这是rRNA启动子转录所需的。在这里,我们讨论了gp67的其他生化见解,噬菌体启动子如何逃避gp67的抑制功能,以及为我们的工作奠定基础的方法进展。
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引用次数: 6
Phage-host interactions during pseudolysogeny: Lessons from the Pid/dgo interaction. 假溶解过程中噬菌体与宿主的相互作用:Pid/dgo 相互作用的启示。
Pub Date : 2013-01-01 Epub Date: 2013-05-21 DOI: 10.4161/bact.25029
William Cenens, Angella Makumi, Mehari Tesfazgi Mebrhatu, Rob Lavigne, Abram Aertsen

Although the study of phage infection has a long history and catalyzed much of our current understanding in bacterial genetics, molecular biology, evolution and ecology, it seems that microbiologists have only just begun to explore the intricacy of phage-host interactions. In a recent manuscript by Cenens et al. we found molecular and genetic support for pseudolysogenic development in the Salmonella Typhimurium-phage P22 model system. More specifically, we observed the existence of phage carrier cells harboring an episomal P22 element that segregated asymmetrically upon subsequent divisions. Moreover, a newly discovered P22 ORFan protein (Pid) able to derepress a metabolic operon of the host (dgo) proved to be specifically expressed in these phage carrier cells. In this addendum we expand on our view regarding pseudolysogeny and its effects on bacterial and phage biology.

尽管噬菌体感染的研究由来已久,并促进了我们目前对细菌遗传学、分子生物学、进化论和生态学的理解,但微生物学家似乎才刚刚开始探索噬菌体-宿主相互作用的复杂性。在 Cenens 等人最近发表的一篇手稿中,我们发现在鼠伤寒沙门氏菌-噬菌体 P22 模型系统中存在假溶解发育的分子和遗传学支持。更具体地说,我们观察到噬菌体载体细胞中存在一种外显的 P22 基因,这种基因在随后的分裂中不对称地分离。此外,一种新发现的 P22 ORFan 蛋白(Pid)能够解除对宿主代谢操作子(dgo)的抑制,并在这些噬菌体载体细胞中特异性表达。在本增编中,我们将进一步阐述假溶质形成及其对细菌和噬菌体生物学的影响。
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引用次数: 0
Lytic bacteriophages reduce Escherichia coli O157: H7 on fresh cut lettuce introduced through cross-contamination. 溶菌噬菌体可减少通过交叉污染引入的新鲜生菜上的大肠杆菌 O157: H7。
Pub Date : 2013-01-01 DOI: 10.4161/bact.24323
Sean Ferguson, Cheryl Roberts, Eric Handy, Manan Sharma

The role of lytic bacteriophages in preventing cross contamination of produce has not been evaluated. A cocktail of three lytic phages specific for E. coli O157:H7 (EcoShield™) or a control (phosphate buffered saline, PBS) was applied to lettuce by either; (1) immersion of lettuce in 500 ml of EcoShield™ 8.3 log PFU/ml or 9.8 log PFU/ml for up to 2 min before inoculation with E. coli O157:H7; (2) spray-application of EcoShield™ (9.3 log PFU/ml) to lettuce after inoculation with E. coli O157:H7 (4.10 CFU/cm2) following exposure to 50 μg/ml chlorine for 30 sec. After immersion studies, lettuce was spot-inoculated with E. coli O157:H7 (2.38 CFU/cm2). Phage-treated, inoculated lettuce pieces were stored at 4°C for and analyzed for E. coli O157:H7 populations for up to 7 d. Immersion of lettuce in 9.8 log PFU/ml EcoShield™ for 2 min significantly (p < 0.05) reduced E. coli O157:H7 populations after 24 h when stored at 4°C compared with controls. Immersion of lettuce in suspensions containing high concentrations of EcoShield™ (9.8 log PFU/ml) resulted in the deposition of high concentrations (7.8 log log PFU/cm2) of bacteriophages on the surface of fresh cut lettuce, potentially contributing to the efficacy of the lytic phages on lettuce. Spraying phages on to inoculated fresh cut lettuce after being washed in hypochlorite solution was significantly more effective in reducing E. coli O157:H7 populations (2.22 log CFU/cm2) on day 0 compared with control treatments (4.10 log CFU/cm2). Both immersion and spray treatments provided protection from E. coli O157:H7 contamination on lettuce, but spray application of lytic bacteriophages to lettuce was more effective in immediately reducing E. coli O157:H7 populations fresh cut lettuce.

尚未评估噬菌体在防止农产品交叉污染方面的作用。将三种针对大肠杆菌 O157:H7 的特异性噬菌体鸡尾酒(EcoShield™)或对照组(磷酸盐缓冲盐水,PBS)应用于生菜,方法是:(1) 将生菜浸泡在 500 毫升 8.3 log PFU/ml 或 9.8 log PFU/ml 的 EcoShield™ 溶液中 2 分钟,然后接种大肠杆菌 O157:H7。8 log PFU/ml 中浸泡 2 分钟;(2) 在接种大肠杆菌 O157:H7 (4.10 CFU/cm2)后,将 EcoShield™ (9.3 log PFU/ml)喷洒在生菜上,然后暴露于 50 μg/ml 氯中 30 秒。浸泡研究后,用大肠杆菌 O157:H7(2.38 CFU/cm2)点滴接种生菜。与对照组相比,将生菜浸泡在 9.8 log PFU/ml EcoShield™ 中 2 分钟可显著减少生菜中大肠杆菌 O157:H7 的数量(p < 0.05)。将生菜浸泡在含有高浓度 EcoShield™ (9.8 log PFU/ml)的悬浮液中,可使高浓度(7.8 log log PFU/cm2)的噬菌体沉积在新切生菜的表面,这可能是溶菌噬菌体对生菜有效的原因。与对照处理(4.10 log CFU/cm2)相比,在次氯酸盐溶液中清洗后向接种的鲜切莴苣上喷洒噬菌体能更有效地减少大肠杆菌 O157:H7 在第 0 天的数量(2.22 log CFU/cm2)。浸泡和喷洒处理都能保护莴苣免受大肠杆菌 O157:H7 的污染,但在莴苣上喷洒噬菌体溶液能更有效地立即减少新鲜切块莴苣上的大肠杆菌 O157:H7 的数量。
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引用次数: 0
Phage therapy: Should bacterial resistance to phages be a concern, even in the long run? 噬菌体治疗:即使从长远来看,细菌对噬菌体的耐药性是否值得关注?
Pub Date : 2013-01-01 DOI: 10.4161/bact.24219
Anni-Maria Ormälä, Matti Jalasvuori

Bacteriophage therapy, the use of viruses that infect bacteria as antimicrobials, has been championed as a promising alternative to conventional antibiotics. Although in the laboratory bacterial resistance against phages arises rapidly, resistance so far has been an only minor problem for the effectiveness of phage therapy. Resistance to antibiotics, however, has become a major issue after decades of extensive use. Should we expect similar problems after long-term use of phages as antimicrobials? Like antibiotics, phages are often noted to be drivers of bacterial evolution. Should we expect phage-treated pathogens to develop a general resistance to phages over time, a resistance against which only, for example, hypothetically co-evolved phages might be infective? Here we argue that the global infection patterns of phages suggest that this is not necessarily a concern as environmental phages often can infect bacteria with which those phages lack any recent co-evolutionary history.

噬菌体疗法,利用感染细菌的病毒作为抗菌剂,一直被认为是传统抗生素的一种有前途的替代品。尽管在实验室中,细菌对噬菌体的耐药性迅速上升,但到目前为止,耐药性只是影响噬菌体治疗有效性的一个小问题。然而,经过几十年的广泛使用,抗生素耐药性已成为一个主要问题。在长期使用噬菌体作为抗菌剂后,我们是否应该期待类似的问题?像抗生素一样,噬菌体通常被认为是细菌进化的驱动力。我们是否应该期望经过噬菌体处理的病原体随着时间的推移对噬菌体产生一种普遍的耐药性,这种耐药性只有,例如,假设共同进化的噬菌体可能具有传染性?在这里,我们认为噬菌体的全球感染模式表明,这并不一定是一个问题,因为环境噬菌体经常可以感染那些噬菌体缺乏任何最近的共同进化历史的细菌。
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引用次数: 60
Dualities in the analysis of phage DNA packaging motors. 噬菌体DNA包装马达分析中的二元性。
Pub Date : 2012-10-01 DOI: 10.4161/bact.23829
Philip Serwer, Wen Jiang

The DNA packaging motors of double-stranded DNA phages are models for analysis of all multi-molecular motors and for analysis of several fundamental aspects of biology, including early evolution, relationship of in vivo to in vitro biochemistry and targets for anti-virals. Work on phage DNA packaging motors both has produced and is producing dualities in the interpretation of data obtained by use of both traditional techniques and the more recently developed procedures of single-molecule analysis. The dualities include (1) reductive vs. accretive evolution, (2) rotation vs. stasis of sub-assemblies of the motor, (3) thermal ratcheting vs. power stroking in generating force, (4) complete motor vs. spark plug role for the packaging ATPase, (5) use of previously isolated vs. new intermediates for analysis of the intermediate states of the motor and (6) a motor with one cycle vs. a motor with two cycles. We provide background for these dualities, some of which are under-emphasized in the literature. We suggest directions for future research.

双链DNA噬菌体的DNA包装马达是分析所有多分子马达的模型,也可用于分析生物学的几个基本方面,包括早期进化、体内与体外生物化学关系和抗病毒靶点。在噬菌体DNA包装马达方面的工作已经并正在对使用传统技术和最近开发的单分子分析程序获得的数据进行二重性解释。这些二元性包括(1)减少与增加演化,(2)电机子组件的旋转与静止,(3)产生力的热棘轮与功率冲程,(4)完整电机与包装atp酶的火花塞作用,(5)使用先前分离的中间体与新的中间体来分析电机的中间状态,(6)一个周期的电机与两个周期的电机。我们为这些二元性提供背景,其中一些在文献中被低估。提出了今后的研究方向。
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引用次数: 18
The moron comes of age. 傻瓜成年了。
Pub Date : 2012-10-01 DOI: 10.4161/bact.23146
Nichole Cumby, Alan R Davidson, Karen L Maxwell

Prophage-encoded genes can provide a variety of benefits for their bacterial hosts. These beneficial genes are often contained within "moron" elements. Morons, thus termed as the insertion of the DNA encoding them adds "more on" the genome in which they are found, are independent transcriptional units disseminated among phage genomes through horizontal gene transfer. Morons have been identified in the majority of phage genomes and they have been found to play diverse roles in bacterial physiology. At present, we are only beginning to ascribe functions to the many proteins encoded within these ubiquitous genetic elements. Recently, we discovered that the first described moron-encoded protein, gp15 of phage HK97, is expressed from the HK97 prophage and functions as a superinfection exclusion protein, protecting its host from genome injection by other phages. This work and the growing body of data pertaining to other morons challenges the traditional view of phages as purely parasites of bacteria and emphasizes the symbiotic relationship between bacteria and prophages.

噬菌体编码的基因可以为它们的细菌宿主提供各种各样的好处。这些有益的基因通常包含在“白痴”元素中。Morons被称为编码它们的DNA的插入,在它们所在的基因组上增加了“更多”,是通过水平基因转移在噬菌体基因组中传播的独立转录单位。在大多数噬菌体基因组中已经发现了Morons,它们在细菌生理学中起着不同的作用。目前,我们才刚刚开始将功能归因于这些无处不在的遗传元件中编码的许多蛋白质。最近,我们发现第一个被描述的非编码蛋白,噬菌体HK97的gp15,从HK97噬菌体中表达,并作为一个重复感染排斥蛋白,保护其宿主免受其他噬菌体的基因组注射。这项工作和越来越多的关于其他傻瓜的数据挑战了噬菌体纯粹是细菌寄生虫的传统观点,并强调了细菌和噬菌体之间的共生关系。
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引用次数: 61
On the interactions between virulent bacteriophages and bacteria in the gut. 肠道内强毒噬菌体与细菌相互作用的研究。
Pub Date : 2012-10-01 DOI: 10.4161/bact.23557
Damien Maura, Laurent Debarbieux

We recently described the targeting of O104:H4 Escherichia coli in mouse gut by several virulent bacteriophages, highlighting several issues relating to virus-host interactions, which we discuss further in this addendum to the original publication.

我们最近描述了几种强毒噬菌体在小鼠肠道中靶向O104:H4大肠杆菌,强调了与病毒-宿主相互作用有关的几个问题,我们在原始出版物的附录中进一步讨论了这些问题。
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引用次数: 26
Soil-based systemic delivery and phyllosphere in vivo propagation of bacteriophages: Two possible strategies for improving bacteriophage persistence for plant disease control. 噬菌体的土壤系统输送和叶球体内繁殖:提高噬菌体持久性以控制植物病害的两种可能策略。
Pub Date : 2012-10-01 DOI: 10.4161/bact.23530
Fanny B Iriarte, Aleksa Obradović, Mine H Wernsing, Lee E Jackson, Botond Balogh, Jason A Hong, M Timur Momol, Jeffrey B Jones, Gary E Vallad

Soil-based root applications and attenuated bacterial strains were evaluated as means to enhance bacteriophage persistence on plants for bacterial disease control. In addition, the systemic nature of phage applied to tomato roots was also evaluated. Several experiments were conducted applying either single phages or phage mixtures specific for Ralstonia solanacearum, Xanthomonas perforans or X. euvesicatoria to soil surrounding tomato plants and measuring the persistence and translocation of the phages over time. In general, all phages persisted in the roots of treated plants and were detected in stems and leaves; although phage level varied and persistence in stems and leaves was at a much lower level compared with persistence in roots. Bacterial wilt control was typically best if the phage or phage mixtures were applied to the soil surrounding tomatoes at the time of inoculation, less effective if applied 3 days before inoculation, and ineffective if applied 3 days after inoculation. The use of an attenuated X. perforans strain was also evaluated to improve the persistence of phage populations on tomato leaf surfaces. In greenhouse and field experiments, foliar applications of an attenuated mutant X. perforans 91-118:∆OPGH strain prior to phage applications significantly improved phage persistence on tomato foliage compared with untreated tomato foliage. Both the soil-based bacteriophage delivery and the use of attenuated bacterial strains improved bacteriophage persistence on respective root and foliar tissues, with evidence of translocation with soil-based bacteriophage applications. Both strategies could lead to improved control of bacterial pathogens on plants.

对基于土壤的根部施用和减毒细菌菌株进行了评估,以提高噬菌体在植物上的持久性,从而控制细菌性疾病。此外,还对番茄根部施用噬菌体的系统性进行了评估。在番茄植株周围的土壤中施用单个噬菌体或噬菌体混合物特异性地抑制茄黑星菌(Ralstonia solanacearum)、穿孔黄单胞菌(Xanthomonas perforans)或欧维西菌(X. euvesicatoria),并测量噬菌体随时间推移的持久性和转移情况。一般来说,所有噬菌体都能在处理过的植物根部存活,在茎和叶中也能检测到噬菌体;但噬菌体的含量各不相同,与根部的存活率相比,茎和叶中的存活率要低得多。如果在番茄接种时将噬菌体或噬菌体混合物施用到番茄周围的土壤中,细菌枯萎病的防治效果通常最好;如果在接种前 3 天施用,则效果较差;如果在接种后 3 天施用,则效果不佳。为了提高噬菌体种群在番茄叶片表面的持久性,还对使用减毒的 X. perforans 菌株进行了评估。在温室和田间试验中,与未经处理的番茄叶片相比,在施用噬菌体之前叶面施用减毒突变体 X. perforans 91-118:∆OPGH 菌株可显著提高噬菌体在番茄叶片上的持久性。基于土壤的噬菌体投放和减毒细菌菌株的使用都提高了噬菌体在根部和叶片组织上的持久性,有证据表明基于土壤的噬菌体施用会发生转运。这两种策略都能改善对植物上细菌病原体的控制。
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引用次数: 0
Life in science: Hans-W. Ackermann. 科学生活:汉斯- w。阿克曼。
Pub Date : 2012-10-01 DOI: 10.4161/bact.23159
Hans-W Ackermann
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引用次数: 11
期刊
Bacteriophage
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