Phage Therapy

噬菌体疗法
  • 文章类型: Journal Article
    细菌有自己的语言,它们像所有高等生物一样彼此交流。所以,许多研究人员正在努力识别和理解这种细菌交流的组成部分,称为群体感应(QS)。在法定感应中,细菌使用称为自动诱导物(AI)的信号分子来交换信息。已经深入研究了许多天然化合物和提取技术以破坏细菌信号并检查其对细菌发病机理控制的有效性。群体感应抑制剂可以干扰QS并阻断AI信号分子的作用。最近的研究表明,群体感应抑制剂(QSI)和群体猝灭酶(QQE)在降低细菌的致病性和抑制生物膜合成方面显示出巨大的前景。此外,证明了QQE和QSI在实验动物模型中的有效性。在创新医疗设备的开发中考虑到这些因素,如敷料和导管,防止细菌感染。本综述重点介绍了这一方面,并对其开发和应用具有前瞻性。
    Bacteria have their own language through which they communicate with one another like all higher organisms. So, many researchers are working hard to identify and comprehend the components of this bacterial communication, known as quorum sensing (QS). In quorum sensing, bacteria use signaling molecules called autoinducers (AIs) to exchange information. Many natural compounds and extraction techniques have been intensively studied to disrupt bacterial signaling and examine their effectiveness for bacterial pathogenesis control. Quorum sensing inhibitors can interfere with QS and block the action of AI signaling molecules. Recent research indicates that quorum sensing inhibitors (QSIs) and quorum quenching enzymes (QQEs) show great promise in reducing the pathogenicity of bacteria and inhibiting biofilm synthesis. In addition, the effectiveness of QQEs and QSIs in experimental animal models was demonstrated. These are taken into account in the development of innovative medical devices, such as dressings and catheters, to prevent bacterial infections. The present review highlights this aspect with a prospective vision for its development and application.
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  • 文章类型: Journal Article
    青枯病(BW)是由土壤传播的细菌青枯病(Rssc)引起的破坏性植物病害。已经做出了许多努力来控制BW,但有效,经济,环保方法仍然不可用。噬菌体是控制细菌性疾病的有前途的资源,包括BW。所以,在这项研究中,分离出一种裂解性噬菌体的作物BW病原体,命名为PQ43W。生物学特性显示PQ43W具有15分钟的短潜伏期,74PFU/cellofbrustsizes,在宽范围的温度和pH值下具有良好的稳定性,但对紫外线辐射的抵抗力较弱。测序显示,噬菌体PQ43W含有47,156bp的环状双链DNA基因组,具有65个预测的开放阅读框(ORF),基因组注释显示PQ43W具有良好的环境安全性,没有tRNA,抗生素耐药性,或含有毒力基因。分类学分类显示,PQ43W属于Caudoviricetes下的Kantovirinae亚科的一个新属。随后,确定了用于控制作物BW的噬菌体疗法的PQ43W剂量:每株植物108PFU*20mL,通过盆栽实验进行两次非侵入性灌溉根部施用。最后,PQ43W的田间试验表明,与常规杀菌剂中生霉素相比,对作物BW的防治效果明显更好。因此,噬菌体PQ43W是控制BW疾病的有效生物防治资源,尤其是作物种植。
    Bacterial wilt (BW) is a devastating plant disease caused by the soil-borne bacterium Ralstonia solanacearum species complex (Rssc). Numerous efforts have been exerted to control BW, but effective, economical, and environmentally friendly approaches are still not available. Bacteriophages are a promising resource for the control of bacterial diseases, including BW. So, in this study, a crop BW pathogen of lytic bacteriophage was isolated and named PQ43W. Biological characterization revealed PQ43W had a short latent period of 15 min, 74 PFU/cell of brust sizes, and good stability at a wide range temperatures and pH but a weak resistance against UV radiation. Sequencing revealed phage PQ43W contained a circular double-stranded DNA genome of 47,156 bp with 65 predicted open reading frames (ORFs) and genome annotation showed good environmental security for the PQ43W that no tRNA, antibiotic resistance, or virulence genes contained. Taxonomic classification showed PQ43W belongs to a novel genus of subfamily Kantovirinae under Caudoviricetes. Subsequently, a dose of PQ43W for phage therapy in controlling crop BW was determined: 108 PFU*20 mL per plant with non-invasive irrigation root application twice by pot experiment. Finally, a field experiment of PQ43W showed a significantly better control effect in crop BW than the conventional bactericide Zhongshengmycin. Therefore, bacteriophage PQ43W is an effective bio-control resource for controlling BW diseases, especially for crop cultivation.
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  • 文章类型: Journal Article
    抗生素的过度使用导致抗生素耐药菌株的出现,比如多重耐药,广泛耐药,和抗pandrug细菌。由这些菌株引起的感染的治疗已经成为一个巨大的挑战。在后抗生素时代,噬菌体疗法是解决这个问题的一个有吸引力的解决方案,一些成功的1期和2期研究已经证明了噬菌体疗法在过去十年中的有效性和安全性。这是进化医学的一种形式,噬菌体表现出免疫调节和抗炎特性。然而,噬菌体疗法受到因素的限制,如宿主菌株的窄谱,体内特殊的药代动力学和药效学,免疫反应,以及噬菌体抗性的发展。本综述的目的是比较裂解噬菌体和化学抗生素治疗细菌感染的效力。噬菌体疗法的优点是副作用少,自我复制,进化,细菌生物膜根除,与化学抗生素相比的免疫调节和抗炎特性。同时,噬菌体疗法的缺点包括可用宿主菌株的窄谱,体内特殊的药代动力学和药效学,免疫反应,和噬菌体抵抗障碍。最近,一些研究人员继续努力克服噬菌体疗法的这些局限性。噬菌体疗法将是治疗抗生素抗性细菌感染的可选方案的一个受欢迎的补充。我们专注于噬菌体疗法的优点和局限性,旨在利用优点并克服局限性。
    The overuse of antibiotics has caused the emergence of antibiotic-resistant strains, such as multidrug-resistant, extensively drug-resistant, and pandrug-resistant bacteria. The treatment of infections caused by such strains has become a formidable challenge. In the post-antibiotic era, phage therapy is an attractive solution for this problem and some successful phase 1 and 2 studies have demonstrated the efficacy and safety of phage therapy over the last decade. It is a form of evolutionary medicine, phages exhibit immunomodulatory and anti-inflammatory properties. However, phage therapy is limited by factors, such as the narrow spectrum of host strains, the special pharmacokinetics and pharmacodynamics in vivo, immune responses, and the development of phage resistance. The aim of this minireview was to compare the potencies of lytic phages and chemical antibiotics to treat bacterial infections. The advantages of phage therapy has fewer side effects, self-replication, evolution, bacterial biofilms eradication, immunomodulatory and anti-inflammatory properties compared with chemical antibiotics. Meanwhile, the disadvantages of phage therapy include the narrow spectrum of available host strains, the special pharmacokinetics and pharmacodynamics in vivo, immune responses, and phage resistance hurdles. Recently, some researchers continue to make efforts to overcome these limitations of phage therapy. Phage therapy will be a welcome addition to the gamut of options available for treating antibiotic-resistant bacterial infections. We focus on the advantages and limitations of phage therapy with the intention of exploiting the advantages and overcoming the limitations.
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  • 文章类型: Journal Article
    多重耐药肺炎克雷伯菌(MDR-KP)在全球医疗保健领域构成了重大挑战。强调创新治疗方法的紧迫性。在抗生素耐药性上升的情况下,噬菌体疗法成为一种有前途的策略,强调鉴定和表征临床使用的有效噬菌体资源的关键需求。在这项研究中,我们介绍了一种新的裂解噬菌体,RCIP0100,由于与已知噬菌体家族的遗传相似性较低,因此根据国际病毒分类学委员会(ICTV)标准将其分类为朝阳病毒属和Fjlabviridae家族。我们的发现表明,RCIP0100对27种测试的MDR-KP菌株中的15种表现出广泛的裂解活性,包括不同的概况,如碳青霉烯类耐药肺炎克雷伯菌(CR-KP)。这将噬菌体RCIP0100定位为噬菌体疗法的有希望的候选者。对RCIP0100耐药的菌株也显示出对各种抗生素的敏感性增加,暗示协同使用RCIP0100和抗生素作为针对MDR-KP的战略对策的潜力。
    Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant challenge in global healthcare, underscoring the urgency for innovative therapeutic approaches. Phage therapy emerges as a promising strategy amidst rising antibiotic resistance, emphasizing the crucial need to identify and characterize effective phage resources for clinical use. In this study, we introduce a novel lytic phage, RCIP0100, distinguished by its classification into the Chaoyangvirus genus and Fjlabviridae family based on International Committee on Taxonomy of Viruses (ICTV) criteria due to low genetic similarity to known phage families. Our findings demonstrate that RCIP0100 exhibits broad lytic activity against 15 out of 27 tested MDR-KP strains, including diverse profiles such as carbapenem-resistant K. pneumoniae (CR-KP). This positions phage RCIP0100 as a promising candidate for phage therapy. Strains resistant to RCIP0100 also showed increased susceptibility to various antibiotics, implying the potential for synergistic use of RCIP0100 and antibiotics as a strategic countermeasure against MDR-KP.
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  • 文章类型: Journal Article
    囊性纤维化(CF)患者容易发生威胁生命的肺部感染,并伴有多种难以根除的病原体,如洋葱伯克霍尔德菌(Bcc),流感嗜血杆菌,脓肿分枝杆菌(Mab),铜绿假单胞菌,和金黄色葡萄球菌。这些感染仍然是一个重要的问题,尽管近年来CF的治疗有了很大改善。此外,长期接触抗生素有利于多重耐药细菌的发展和传播;因此,替代策略的制定对于对抗抗菌素耐药性至关重要.在这种情况下,噬菌体疗法,即,噬菌体的使用,特别感染细菌的病毒,已经成为一种有前途的战略。在这次审查中,我们的目标是解决噬菌体疗法在多重耐药感染管理中的现状,从富有同情心的用例到正在进行的临床试验,以及这种方法在CF患者的特殊情况下所面临的挑战。
    Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as Burkholderia cepacia complex (Bcc), Hemophilus influenzae, Mycobacterium abscessus (Mab), Pseudomonas aeruginosa, and Staphylococcus aureus. These infections still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure to antibiotics in combination favors the development and spread of multi-resistant bacteria; thus, the development of alternative strategies is crucial to counter antimicrobial resistance. In this context, phage therapy, i.e., the use of phages, viruses that specifically infect bacteria, has become a promising strategy. In this review, we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.
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  • 文章类型: Journal Article
    在全球抗生素耐药性危机升级的情况下,噬菌体正在成为对抗抗生素耐药性细菌的有希望的替代品。最近,对噬菌体的兴趣有了明显的恢复,促使人们对其治疗潜力进行广泛的研究。除了传统的微生物学和病毒学技术,如基因组学和蛋白质组学,正在探索新的表型和化学表征方法。其中,对振动光谱学的兴趣越来越大,特别是在先进的模式,如表面增强拉曼光谱(SERS),尖端增强拉曼光谱(TERS),和原子力显微镜-红外光谱(AFM-IR),提供改进的灵敏度和空间分辨率。这篇综述探讨了振动光谱在噬菌体中的用途,包括它在诊断中的作用,生物传感,噬菌体检测,协助以噬菌体为基础的治疗,推进基础研究。
    Bacteriophages are emerging as a promising alternative in combating antibiotic-resistant bacteria amidst the escalating global antimicrobial resistance crisis. Recently, there has been a notable resurgence of interest in phages, prompting extensive research into their therapeutic potential. Beyond conventional microbiology and virology techniques, such as genomics and proteomics, novel phenotypic and chemical characterization methods are being explored. Among these, there is a growing interest in vibrational spectroscopy, especially in advanced modalities such as surface-enhanced Raman spectroscopy (SERS), tip-enhanced Raman spectroscopy (TERS), and atomic force microscopy-infrared spectroscopy (AFM-IR), which offer improved sensitivity and spatial resolution. This review explores the spectrum of uses of vibrational spectroscopy for bacteriophages, including its role in diagnostics, biosensing, phage detection, assistance in phage-based therapy, and advancing basic research.
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  • 文章类型: Journal Article
    背景:噬菌体(噬菌体)疗法是一种有前途的替代抗菌方法,它有可能改变我们治疗细菌感染的方式。抗生素耐药性危机正在推动人们对噬菌体疗法的新兴趣。目前没有许可的噬菌体疗法药物产品,并且在未经许可的基础上,以少量但不断增长的患者数量使用噬菌体疗法。
    目的:本文为英国的临床医生提供了有关患者无证噬菌体疗法适用性评估的指南。
    方法:本文建立在苏格兰健康改善建议的基础上,考虑在难以治疗的感染中使用噬菌体疗法,以及作者小组的经验,他们共同评估了30名患者的适用性噬菌体疗法。
    背景:在英国,无证药品,包括噬菌体,可以考虑满足特殊的临床需求。无证药品的使用受国家立法和当地NHS信托政策的约束。噬菌体可用于任何NHS信托,有关适用性的决定应通过现有的当地临床管理途径做出。本文制定了指南,以支持当地临床团队评估患者对噬菌体疗法的适用性。介绍了临床和微生物学方面的考虑,包括过敏和怀孕。
    BACKGROUND: Bacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licenced phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis.
    OBJECTIVE: This article provides guidelines on the assessment of patient suitability for unlicensed phage therapy for clinicians in the United Kingdom.
    METHODS: This article builds on Health Improvement Scotland\'s recommendation for the consideration of phage therapy in difficult-to-treat infection and the experience of the author group who have collectively assessed the suitability of 30 patients for phage therapy.
    BACKGROUND: In the UK, unlicensed medicines, including phages, may be considered to meet special clinical needs. The use of unlicensed medicines is governed by national legislation and local NHS Trust policies. Phages can be used in any NHS Trust and decisions about suitability should be made via existing local clinical management pathways. This article sets out guidelines to support local clinical teams in the assessment of patient suitability for phage therapy. Clinical and microbiological considerations are presented, including allergy and pregnancy.
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  • 文章类型: Journal Article
    传染病导致显著的发病率和死亡率。通常,疾病急性期的解决导致微生物的持久性,导致慢性衰弱的疾病。持续感染的管理通常需要使用抗菌药物进行终身治疗。这些感染可能是慢性病毒感染,如艾滋病毒,乙型肝炎或慢性细菌持续感染,如由多药耐药生物引起的人工关节感染。噬菌体是专门针对顽固性细菌感染而设计的,如人工关节感染不同的成功。在这次审查中,我们描述了使用感染剂治疗其他持续性感染的创新疗法相关情景和风险的历史演变.
    [方框:见正文]。
    Infectious diseases lead to significant morbidity and mortality. Often, resolution of the acute stage of the disease leads to microbial persistence, resulting in chronic debilitating disease. Management of persistent infections frequently requires lifelong therapy with antimicrobial agents. These infections could be chronic viral infections like HIV, hepatitis B or chronic bacterial persistent infections like prosthetic joint infections caused by multi-drug resistant organisms. Bacteriophages have been designed specifically to target recalcitrant bacterial infections, such as prosthetic joint infections with varying success. In this review, we describe the historic evolution of scenarios and risks associated with innovative therapy using infectious agents to treat other persistent infections.
    [Box: see text].
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  • 文章类型: Journal Article
    约翰病(JD),一个慢性的,由鸟分枝杆菌亚种引起的感染性肠炎。副结核病(MAP),影响野生和家养反刍动物。没有治愈或有效的预防,目前的疫苗有很大的局限性,使这种疾病在所有重要的乳制品行业中广泛传播,和动物福利的影响。近年来,分枝杆菌噬菌体(MP)已引起人们的兴趣,并被提出作为减少MAP感染的有希望的解决方案。使用经过充分验证的感染模型,我们已经证明了MPs在保护奶牛免受MAP感染方面的预防潜力.从出生到2m龄断奶,每天给小牛补充噬菌体混合物,并在2周龄接种MAP。通过血液测量4.5个月的感染状态,粪便,和尸体组织样本.我们的发现强调了口服MPs的显着功效。值得注意的是,在10周内完全消除了MAP的粪便脱落,与感染的对照组相反,在整个试验期间都持续脱落。死后组织培养分析进一步支持了MPs的有效性,与感染对照组中6只动物中的6只相比,噬菌体处理组中6只动物中只有1只对MAP定殖组织测试为阳性。此外,菌斑测定结果证明了噬菌体在肠道内持续存在的能力。总的来说,这些结果强调了口服MP鸡尾酒作为一种高效的干预策略的潜力,可以对抗乳牛和乳制品行业的JD.
    Johne\'s disease (JD), a chronic, infectious enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), affects wild and domestic ruminants. There is no cure or effective prevention, and current vaccines have substantial limitations, leaving this disease widespread in all substantial dairy industries causing economic, and animal welfare implications. Mycobacteriophages (MPs) have been gaining interest in recent years and are proposed as a promising solution to curtailing MAP infection. Using a well-validated infection model, we have demonstrated the preventative potential of MPs to protect dairy calves against MAP infection. Calves were supplemented daily with a phage cocktail from birth till weaning at 2 m of age and inoculated with MAP at 2 wk of age. Infection status was measured for 4.5 mo through blood, fecal, and postmortem tissue samples. Our findings highlight the remarkable efficacy of orally administered MPs. Notably, fecal shedding of MAP was entirely eliminated within 10 wk, in contrast to the infected control group where shedding continued for the entirety of the trial period. Postmortem tissue culture analysis further supported the effectiveness of MPs, with only 1 out of 6 animals in the phage-treated group testing positive for MAP colonized tissues compared to 6 out of 6 animals in the infected control group. Additionally, plaque assay results demonstrated the ability of phages to persist within the intestinal tract. Collectively, these results underscore the potential of orally administered MP cocktails as a highly effective intervention strategy to combat JD in dairy calves and by extension in the dairy industry.
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  • 文章类型: Journal Article
    抗菌素耐药性(AMR)是全球关注的主要问题;抗生素和其他常规治疗方法未能克服不断增加的传染病。噬菌体(噬菌体)是特异性靶向/杀死细菌宿主而不影响其他人类微生物组的病毒。噬菌体疗法在当前的全球医疗保健方案中提供了乐观,其在人类中的应用历史悠久,现已进行了各种临床试验。临床试验中的噬菌体有特定的要求是完全溶解的,没有毒性基因,具有增强的宿主范围,这增加了这一必要条件的优势。这篇综述详细解释了各种噬菌体工程方法及其在治疗中的潜在应用。为了使噬菌体更有效,工程已经尝试使用传统的同源重组技术,电穿孔DNA(BRED)的噬菌体重组,成簇的规则间隔短回文重复(CRISPR)-Cas,具有感染性颗粒(BRIP)的CRISPY-BRED/噬菌体重组,化学加速病毒进化(CAVE),和噬菌体基因组重启。噬菌体以鸡尾酒的形式与抗生素联合使用,疫苗,和纯化的蛋白质,例如内溶素。因此,噬菌体疗法被证明是治疗危及生命的感染的更好选择,具有更多的特异性和更少的有害后果。
    Antimicrobial resistance (AMR) is a major global concern; antibiotics and other regular treatment methods have failed to overcome the increasing number of infectious diseases. Bacteriophages (phages) are viruses that specifically target/kill bacterial hosts without affecting other human microbiome. Phage therapy provides optimism in the current global healthcare scenario with a long history of its applications in humans that has now reached various clinical trials. Phages in clinical trials have specific requirements of being exclusively lytic, free from toxic genes with an enhanced host range that adds an advantage to this requisite. This review explains in detail the various phage engineering methods and their potential applications in therapy. To make phages more efficient, engineering has been attempted using techniques like conventional homologous recombination, Bacteriophage Recombineering of Electroporated DNA (BRED), clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, CRISPY-BRED/Bacteriophage Recombineering with Infectious Particles (BRIP), chemically accelerated viral evolution (CAVE), and phage genome rebooting. Phages are administered in cocktail form in combination with antibiotics, vaccines, and purified proteins, such as endolysins. Thus, phage therapy is proving to be a better alternative for treating life-threatening infections, with more specificity and fewer detrimental consequences.
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