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phage therapy

Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Kamal Veisi, Shiva Ahdi Khosroshahi, Asghar Tanomand
Epidermal growth factor receptor (EGFR) as a transmembrane tyrosine kinase receptor is frequently overexpresses in tumors with epithelial origin. The L2 domain from extracellular part of EGFR is involved in ligand binding and the blockage of this domain prevents activation of related signaling pathways. This study was aimed to develop a novel human scFv against EGFR L2 domain as a promising target for cancer therapy. The L2 recombinant protein was purified and used for panning a human scFv phage library (Tomlinson I)...
September 28, 2016: Current Pharmaceutical Design
Elsa Bodier-Montagutelli, Eric Morello, Guillaume l'Hostis, Antoine Guillon, Emilie Dalloneau, Renaud Respaud, Nikita Pallaoro, Hélène Blois, Laurent Vecellio, Jérôme Gabard, Nathalie Heuzé-Vourc'h
Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context...
October 25, 2016: Expert Opinion on Drug Delivery
Jessica M Andriolo, Richard J Rossi, Casey A McConnell, Baili I Connors, Kevin Trout, M K Hailer, Marisa L Pedulla, Jack L Skinner
The Centers for Disease Control and Prevention have estimated that each year, two million people in the United States become infected with antibiotic-resistant bacteria, of which, approximately 23 000 die as a direct result of these infections. Phage therapy, or the treatment of bacterial infection by specific, antagonistic viruses, provides one alternative to traditional antibiotics. Bacteriophages, or phages, are bacteriaspecific viruses that possess biological traits that allow for not only the removal of bacterial infection, but also the evasion of bacterial resistance which renders antibiotics ineffective...
October 19, 2016: IEEE Transactions on Nanobioscience
Mor Shlezinger, Yael Houri-Haddad, Shunit Coppenhagen-Glazer, Grégory Resch, Yok-Ai Que, Shaul Beyth, Elisheva Dorfman, Ronen Hazan, Nurit Beyth
Dental diseases are perhaps the most prevalent infection-related diseases in humans. Biofilm is involved in almost every infectious disease compromising oral health, notably caries, periodontal disease, gingivitis, endodontic infections and peri-implantitis. Current therapies of biofilm-derived oral infections lack sensitivity; they are not species-specific and kill pathogenic species as well as commensal species, which are protective against the formation of pathogenic biofilms. Moreover, antibiotics have a limited effect on biofilm and are almost unused in oral diseases...
September 30, 2016: Current Topics in Medicinal Chemistry
Chong Chen, Kun Liu, Yupeng Xu, Pengwei Zhang, Yan Suo, Yi Lu, Wenyuan Zhang, Li Su, Qing Gu, Huamao Wang, Jianren Gu, Zonghai Li, Xun Xu
Anti-vascular endothelial growth factor (VEGF) therapies are widely used for the treatment of neovascular fundus diseases such as diabetic retinopathy. However, these agents need to be injected intravitreally, because their strong hydrophilicity and high molecular weight prevent them from penetrating cell membranes and complex tissue barriers. Moreover, the repeated injections that are required can cause infection and tissue injury. In this study, we used in vivo-directed evolution phage display technology to identify a novel dodecapeptide, named CC12, with the ability to penetrate the ocular barrier in a noninvasive (via conjunctival sac instillation) or minimally invasive (via retrobulbar injection) manner...
September 30, 2016: Biomaterials
Ia Kusradze, Natia Karumidze, Sophio Rigvava, Teona Dvalidze, Malkhaz Katsitadze, Irakli Amiranashvili, Marina Goderdzishvili
Acinetobacter baumannii is a gram-negative, non-motile bacterium that, due to its multidrug resistance, has become a major nosocomial pathogen. The increasing number of multidrug resistant (MDR) strains has renewed interest in phage therapy. The aim of our study was to assess the effectiveness of phage administration in Acinetobacter baumannii wound infections in an animal model to demonstrate phage therapy as non-toxic, safe and alternative antibacterial remedy. Using classical methods for the study of bacteriophage properties, we characterized phage vB-GEC_Ab-M-G7 as a dsDNA myovirus with a 90 kb genome size...
2016: Frontiers in Microbiology
Matthew L Paff, Scott L Nuismer, Andrew D Ellington, Ian J Molineux, Ryan H May, James J Bull
BACKGROUND: We propose, model, and implement a novel system of population-level intervention against a virus. One context is a treatment against a chronic infection such as HIV. The underlying principle is a form of virus 'wars' in which a benign, transmissible agent is engineered to protect against infection by and spread of a lethal virus. In our specific case, the protective agent consists of two entities, a benign virus and a gene therapy vector mobilized by the benign virus. RESULTS: Numerical analysis of a mathematical model identified parameter ranges in which adequate, population-wide protection is achieved...
2016: Journal of Biological Engineering
S A Sarker, B Berger, Y Deng, S Kieser, F Foata, D Moine, P Descombes, S Sultana, S Huq, P K Bardhan, V Vuillet, F Praplan, H Brüssow
A T4-like coliphage cocktail was given with different oral doses to healthy Bangladeshi children in a placebo-controlled randomized phase I safety trial. Fecal phage detection was oral dose dependent suggesting passive gut transit of coliphages through the gut. No adverse effects of phage application were seen clinically and by clinical chemistry. Similar results were obtained for a commercial phage preparation (Coliproteus from Microgen/Russia). By 16S rRNA gene sequencing only a low degree of fecal microbiota conservation was seen in healthy children from Bangladesh who were sampled over a time interval of 7 days suggesting a substantial temporal fluctuation of the fecal microbiota composition...
October 17, 2016: Environmental Microbiology
Yin-Ku Liang, Liu-Jiao Bian
Kringle 5, the fifth fragment of plasminogen, is known to be important for inhibiting the proliferation and migration of vascular endothelial cell (VEC), while not having any effects on normal endothelial cells. Therefore, it may be a potential tumor therapy candidate. However, the ligand of the Kringle 5 in VEC has not yet been identified. In this study, the possible ligand of Kringle 5 in vitro was screened and validated using Ph.D.-7 phage display peptide library with molecular docking, along with surface plasma resonance (SPR)...
2016: PloS One
Stephen T Abedon
The concept of bacteriophage multiplicity of infection (MOI) - ratios of phages to bacteria - historically has been less easily applied than many phage workers would prefer or, perhaps, may be aware. Here, toward clarification of the concept, I discuss multiplicity of infection in terms of semantics, history, mathematics, pharmacology, and actual practice. For phage therapy and other biocontrol purposes it is desirable, especially, not to solely employ MOI to describe what phage quantities have been applied during dosing...
July 2016: Bacteriophage
Yingying Hong, Jyothi Thimmapuram, Jiayi Zhang, Clayton K Collings, Ketaki Bhide, Kyle Schmidt, Paul D Ebner
Numerous studies have shown the efficacy of phage therapy in reducing foodborne pathogen carriage in food animals. Fewer studies have focused on host reactions, especially in terms of phage-mediated acute immune responses and effects on the gut microbiome. Here we administered E. coli O157:H7 phages in low (single dose of 10(5) PFU) or high (single dose of 10(7) PFU) quantities to mice. While there were time points at which cytokine levels in different treatment groups differed from one another, all cytokine levels remained within normal ranges for mice regardless of treatment...
July 2016: Bacteriophage
Carmen Burtea, Sophie Laurent, Tuba Sanli, Deborah Fanfone, Aude Devalckeneer, Sébastien Sauvage, Marie-Claire Beckers, Sandrine Rorive, Isabelle Salmon, Luce Vander Elst, Bernard R Lauwerys, Robert N Muller
BACKGROUND: Interleukin-7 receptor alpha (IL-7Rα) represents a biomarker with potential applications in rheumatoid arthritis (RA) diagnosis and therapy. We have therefore searched by phage display potential IL-7Rα specific peptides with the primary goal being to develop in vivo molecular imaging tools. METHODS: IL-7Rα-targeted peptides were searched within a disulfide-constrained combinatorial phage displayed library of random linear heptapeptides. The apparent dissociation constant (Kd) and half maximal inhibition constant (IC50) were estimated for phage clones and synthesized peptides by ELISA...
October 12, 2016: Arthritis Research & Therapy
Andrzej Górski, Ryszard Międzybrodzki, Beata Weber-Dąbrowska, Wojciech Fortuna, Sławomir Letkiewicz, Paweł Rogóż, Ewa Jończyk-Matysiak, Krystyna Dąbrowska, Joanna Majewska, Jan Borysowski
Antimicrobial resistance is considered to be one of the greatest challenges of medicine and our civilization. Lack of progress in developing new anti-bacterial agents has greatly revived interest in using phage therapy to combat antibiotic-resistant infections. Although a number of clinical trials are underway and more are planned, the realistic perspective of registration of phage preparations and their entering the health market and significantly contributing to the current antimicrobial crisis is rather remote...
2016: Frontiers in Microbiology
Xiangna Zhao, Mikael Skurnik
Bacteriophage play many varied roles in microbial ecology and evolution. This chapter collates a vast body of knowledge and expertise on Yersinia pestis phages, including the history of their isolation and classical methods for their isolation and identification. The genomic diversity of Y. pestis phage and bacteriophage islands in the Y. pestis genome are also discussed because all phage research represents a branch of genetics. In addition, our knowledge of the receptors that are recognized by Y. pestis phage, advances in phage therapy for Y...
2016: Advances in Experimental Medicine and Biology
Sonika Sharma, Soumya Chatterjee, Sibnarayan Datta, Rishika Prasad, Dharmendra Dubey, Rajesh Kumar Prasad, Mohan G Vairale
Bacteriophages (or phages), the most abundant viral entity of the planet, are omni-present in all the ecosystems. On the basis of their unique characteristics and anti-bacterial property, phages are being freshly evaluated taxonomically. Phages replicate inside the host either by lytic or lysogenic mode after infecting and using the cellular machinery of a bacterium. Since their discovery by Twort and d'Herelle in the early 1900s, phage became an important agent for combating pathogenic bacteria in clinical treatments and its related research gained momentum...
October 8, 2016: Folia Microbiologica
Jan Müller, Robin Reichel, Sebastian Vogt, Stefan P Müller, Wolfgang Sauerwein, Wolfgang Brandau, Angelika Eggert, Alexander Schramm
Neuroectodermal tumours are characterized by aberrant processing of disialogangliosides concomitant with high expression of GD2 or GD3 on cell surfaces. Antibodies targeting GD2 are already in clinical use for therapy of neuroblastoma, a solid tumour of early childhood. Here, we set out to identify peptides with high affinity to human disialoganglioside GD2. To this end, we performed a combined in vivo and in vitro screen using a recombinant phage displayed peptide library. We isolated a phage displaying the peptide sequence WHWRLPS that specifically binds to the human disialoganglioside GD2...
2016: PloS One
Nattan Stalin, Pappu Srinivasan
Phage therapy is an alternative and eco-friendly biocontrol agent to prevent and control multidrug resistant bacteria in the aquatic system. The aim of this study is to isolate and characterize the Vibrio parahaemolyticus and its potential lytic phage from Penaeus monodon growing-out by rearing in shrimp ponds in Palk Strait, South East coast of India. The conventional phenotypic characteristics and molecular identification was confirmed using 16S rRNA sequence and to determine the antibiotic resistant profiles...
September 30, 2016: Biologicals: Journal of the International Association of Biological Standardization
Carla Pereira, Catarina Moreirinha, Luís Teles, Rui J M Rocha, Ricardo Calado, Jesús L Romalde, Maria L Nunes, Adelaide Almeida
The present study investigated the potential application of the bacteriophage (or phage) phT4A, ECA2 and the phage cocktail phT4A/ECA2 to decrease the concentration of Escherichia coli during the depuration of natural and artificially contaminated cockles. Depuration in static seawater at multiplicity of infection (MOI) of 1 with single phage suspensions of phT4A and ECA2 was the best condition, as it decreased by ∼2.0 log CFU/g the concentration of E. coli in artificially contaminated cockles after a 4 h of treatment...
February 2017: Food Microbiology
Sanne A M van Lith, Ilse Roodink, Joost J C Verhoeff, Petri I Mäkinen, Jari P Lappalainen, Seppo Ylä-Herttuala, Jos Raats, Erwin van Wijk, Ronald Roepman, Stef J Letteboer, Kiek Verrijp, William P J Leenders
Diffuse gliomas are primary brain cancers that are characterised by infiltrative growth. Whereas high-grade glioma characteristically presents with perinecrotic neovascularisation, large tumor areas thrive on pre-existent vasculature as well. Clinical studies have revealed that pharmacological inhibition of the angiogenic process does not improve survival of glioblastoma patients. Direct targeting of tumor vessels may however still be an interesting therapeutic approach as it allows pinching off the blood supply to tumor cells...
September 26, 2016: Oncotarget
Hugo Oliveira, Graça Pinto, Ana Oliveira, Carla Oliveira, Maria Alberta Faustino, Yves Briers, Lucília Domingues, Joana Azeredo
Citrobacter spp., although frequently ignored, is emerging as an important nosocomial bacterium able to cause various superficial and systemic life-threatening infections. Considered to be hard-to-treat bacterium due to its pattern of high antibiotic resistance, it is important to develop effective measures for early and efficient therapy. In this study, the first myovirus (vB_CfrM_CfP1) lytic for Citrobacter freundii was microbiologically and genomically characterized. Its morphology, activity spectrum, burst size, and biophysical stability spectrum were determined...
September 28, 2016: Applied Microbiology and Biotechnology
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