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https://www.readbyqxmd.com/read/29330364/polypharmacy-through-phage-display-selection-of-glucagon-and-glp-1-receptor-co-agonists-from-a-phage-displayed-peptide-library
#1
Anna Demartis, Armin Lahm, Licia Tomei, Elisa Beghetto, Valentina Di Biasio, Federica Orvieto, Francesco Frattolillo, Paul E Carrington, Sheena Mumick, Brian Hawes, Elisabetta Bianchi, Anandan Palani, Antonello Pessi
A promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318563/generation-of-highly-selective-mmp-antibody-inhibitors
#2
Dong Hyun Nam, Xin Ge
Inhibiting individual MMPs of biomedical importance with high selectivity is critical for both fundamental research and therapy development. Here we describe the methods for discovery of inhibitory monoclonal antibodies from synthetic human antibody phage display libraries carrying convex paratopes encoded by long complementarity-determining region (CDR)-H3 segments. We demonstrate the application of this technique for isolation of highly specific and potent antibody inhibitors of human MMP-14.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29317070/hypothesis-for-the-cause-and-therapy-of-neurodegenerative-diseases
#3
Philip Serwer
The cause and therapy of neurodegenerative diseases remain unsolved puzzles. These diseases are correlated with presence of beta sheet-rich amyloid assemblies. Here, I derive and assemble puzzle pieces to obtain a loose end-tying hypothesis for cause with direct implications for therapy. I use the following extrapolations to find connectable puzzle pieces: (a) the traditional extrapolation that amyloid/amyloid precursors cause disease, (b) a recent extrapolation that amyloid-forming proteins, some of which are virus protein homologs, are components of an empirically obscure innate immune system that counters insults, including those by both viruses and bacteria, (c) a new extrapolation that various insults produce assemblies with structural features in common and that amyloid-forming, innate immune system proteins recognize these features and, then, counter insults by co-assembly, (d, 1) a second new extrapolation that beta sheet is a common structural feature and is extended during insult-neutralizing co-assembly and (d, 2) an appendix, derived from studies of phages T3 and T4, that most insult-produced assemblies are obscure to current biochemical analysis...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29315249/bacteriophage-%C3%AE-sa012-has-a-broad-host-range-against-staphylococcus-aureus-and-effective-lytic-capacity-in-a-mouse-mastitis-model
#4
Hidetomo Iwano, Yusuke Inoue, Takuji Takasago, Hironori Kobayashi, Takaaki Furusawa, Kotomi Taniguchi, Jumpei Fujiki, Hiroshi Yokota, Masaru Usui, Yasunori Tanji, Katsuro Hagiwara, Hidetoshi Higuchi, Yutaka Tamura
Bovine mastitis is an inflammation of the mammary gland caused by bacterial infection in dairy cattle. It is the most costly disease in the dairy industry because of the high use of antibiotics. Staphylococcus aureus is one of the major causative agents of bovine mastitis and antimicrobial resistance. Therefore, new strategies to control bacterial infection are required in the dairy industry. One potential strategy is bacteriophage (phage) therapy. In the present study, we examined the host range of previously isolated S...
January 9, 2018: Biology
https://www.readbyqxmd.com/read/29301897/complete-genome-sequences-of-three-bacillus-anthracis-bacteriophages
#5
Sivan Alkalay, Sarit Sternberg, Shunit Coppenhagen-Glazer, Ronen Hazan
The new highly effective Bacillus anthracis phages Negev_SA, Carmel_SA, and Tavor_SA were isolated from soil samples, and their complete genomes were sequenced and analyzed. The isolated phages have potential use in future phage therapy treatment against anthrax.
January 4, 2018: Genome Announcements
https://www.readbyqxmd.com/read/29298913/cross-genus-rebooting-of-custom-made-synthetic-bacteriophage-genomes-in-l-form-bacteria
#6
Samuel Kilcher, Patrick Studer, Christina Muessner, Jochen Klumpp, Martin J Loessner
Engineered bacteriophages provide powerful tools for biotechnology, diagnostics, pathogen control, and therapy. However, current techniques for phage editing are experimentally challenging and limited to few phages and host organisms. Viruses that target Gram-positive bacteria are particularly difficult to modify. Here, we present a platform technology that enables rapid, accurate, and selection-free construction of synthetic, tailor-made phages that infect Gram-positive bacteria. To this end, custom-designed, synthetic phage genomes were assembled in vitro from smaller DNA fragments...
January 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29298884/genomic-and-biochemical-characterization-of-acinetobacter-podophage-petty-reveals-a-novel-lysis-mechanism-and-tail-associated-depolymerase-activity
#7
A C Hernandez-Morales, L L Lessor, T L Wood, D Migl, E M Mijalis, W K Russell, R F Young, J J Gill
The increased prevalence of drug-resistant, nosocomial Acinetobacter infections, particularly from pathogenic members of the Acinetobacter calcoaceticus-baumannii complex, necessitates the exploration of novel treatments such as phage therapy. In the present study, we characterize phage Petty, a novel podophage that infects multidrug-resistant Acinetobacter nosocomialis and Acinetobacter baumannii Genome analysis reveals that phage Petty is a 40,431bp ϕKMV-like phage, with a coding density of 92.2% and a G+C content of 42...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29295549/comparative-analysis-of-37-acinetobacter-bacteriophages
#8
Dann Turner, Hans-Wolfgang Ackermann, Andrew M Kropinski, Rob Lavigne, J Mark Sutton, Darren M Reynolds
Members of the genus Acinetobacter are ubiquitous in the environment and the multiple-drug resistant species A. baumannii is of significant clinical concern. This clinical relevance is currently driving research on bacterial viruses infecting A. baumannii, in an effort to implement phage therapy and phage-derived antimicrobials. Initially, a total of 42 Acinetobacter phage genome sequences were available in the international nucleotide sequence databases, corresponding to a total of 2.87 Mbp of sequence information and representing all three families of the order Caudovirales and a single member of the Leviviridae...
December 24, 2017: Viruses
https://www.readbyqxmd.com/read/29288451/phage-therapy-various-perspectives-on-how-to-improve-the-art
#9
Stephen T Abedon
Use of phages as antibacterial agents has a long and, even, storied history. During that time much has been learned but, to a degree, also forgotten. As a consequence, today we experience a largely preclinical development of a field which already has been subject to substantial clinical practice. This development, as well, is now occurring within a much more rigorously regulated environment than previously had been the case. The consequence is not only a need to reinvent standards of practice but to do so within a more explicitly pharmacological context...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29285351/application-of-phage-display-for-the-development-of-a-novel-inhibitor-of-pla2-activity-in-western-cottonmouth-venom
#10
James K Titus, Matthew K Kay, Cdr Jacob J Glaser
Snakebite envenomation is an important global health concern. The current standard treatment approach for snakebite envenomation relies on antibody-based antisera, which are expensive, not universally available, and can lead to adverse physiological effects. Phage display techniques offer a powerful tool for the selection of phage-expressed peptides, which can bind with high specificity and affinity towards venom components. In this research, the amino acid sequences of Phospholipase A2 (PLA2) from multiple cottonmouth species were analyzed, and a consensus peptide synthesized...
2017: Journal of Venom Research
https://www.readbyqxmd.com/read/29283323/phage-therapy-against-streptococcus-pneumoniae-modern-tool-to-control-pneumonia
#11
Muhammad Imran Qadir, Sahir Sajjad
Phage therapy is important for treatment of drug-resistant pathogens as compared to antibiotics in this modern era. Since 1966, bacteriophages have been used as antibacterial agents and played a very crucial role in the expansion of molecular biology. Bacteriophages have been used to treat infection in Western medicine along with antibiotics. Antibacterial agents against the antibiotic resistance strains have been discovered. The lytic bacteriophage used for treatment in conventional phage therapy have shown hopeful results in human clinical cases...
2017: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29282504/bacteriophages-as-biological-control-agents-of-enteric-bacteria-contaminating-edible-oysters
#12
Tuan Son Le, Paul C Southgate, Wayne O'Connor, Sue Poole, D Ipek Kurtbӧke
Bacterial contamination on seafood resulting from unhygienic food-handling practices causes foodborne diseases and significant revenue losses. Moreover, control measures are complicated by a high prevalence of antibiotic-resistant bacteria. Alternative measures such as the phage therapy, therefore, is considered as an environmental and consumer-friendly biological control strategy for controlling such bacterial contamination. In this study, we determined the effectiveness of a bacteriophage cocktail in controlling E...
December 27, 2017: Current Microbiology
https://www.readbyqxmd.com/read/29276570/complete-genome-of-a-novel-virulent-phage-st0-lysing-escherichia-coli-h8
#13
Honghui Liu, Xinchun Liu, Jinqing Li
Phage ST0 lysing Escherichia coli H8 was isolated from wastewater and sequenced using an Illumina HiSeq system. Genomic analyses revealed that it was virulent phages and contained a circular double-stranded DNA genome, consisting of 170,496 nucleotides with an average G + C content of 37.67%. This study may provide possible alternative materials for phage therapy.
2017: Standards in Genomic Sciences
https://www.readbyqxmd.com/read/29276503/synergistic-antimicrobial-interaction-between-honey-and-phage-against-escherichia-coli-biofilms
#14
Ana Oliveira, Henrique G Ribeiro, Ana C Silva, Maria D Silva, Jessica C Sousa, Célia F Rodrigues, Luís D R Melo, Ana F Henriques, Sanna Sillankorva
Chronic wounds afford a hostile environment of damaged tissues that allow bacterial proliferation and further wound colonization. Escherichia coli is among the most common colonizers of infected wounds and it is a prolific biofilm former. Living in biofilm communities, cells are protected, become more difficult to control and eradicate, and less susceptible to antibiotic therapy. This work presents insights into the proceedings triggering E. coli biofilm control with phage, honey, and their combination, achieved through standard antimicrobial activity assays, zeta potential and flow cytometry studies and further visual insights sought by scanning electron microscopy and transmission electron microscopy...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29240296/bacteriophage-effectively-kills-multidrug-resistant-staphylococcus-aureus-clinical-isolates-from-chronic-rhinosinusitis-patients
#15
Guimin Zhang, Yin Zhao, Sathish Paramasivan, Katharina Richter, Sandra Morales, Peter-John Wormald, Sarah Vreugde
BACKGROUND: Bacteriophage (phage) therapy has been proposed as an alternative to antibiotics. Phages have been shown to kill antibiotic resistant Staphylococcus aureus strains; however, it is unknown whether stress-induced antibiotic tolerance affects S. aureus susceptibility to phages. Our objective was to determine the effectiveness of 2 phages currently in clinical development, against antibiotic-resistant and induced antibiotic-tolerant clinical S. aureus isolates. METHODS: Antibiotic tolerant S...
December 14, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29234314/efficacy-and-safety-of-a-bovine-associated-staphylococcus-aureus-phage-cocktail-in-a-murine-model-of-mastitis
#16
Koen Breyne, Ryan W Honaker, Zachary Hobbs, Manuela Richter, Maciej Żaczek, Taylor Spangler, Jonas Steenbrugge, Rebecca Lu, Anika Kinkhabwala, Bruno Marchon, Evelyne Meyer, Lucia Mokres
Overuse of antibiotics is a major problem in the treatment of bovine mastitis, and antibiotic treatment is frequently non-curative, thus alternative treatments are necessary. The primary aim of this study was to evaluate the efficacy of a purified phage cocktail for treatment of bovine Staphylococcus aureus mastitis in a well-defined mouse model. Candidate phages were selected based on their in vitro performance and subsequently processed into an optimally composed phage cocktail. The highest scoring phages were further tested for efficacy and resistance suppression in broth and raw milk, with and without supplemental IgG...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29231827/phage-therapy-revival-of-the-bygone-antimicrobial
#17
Geoff Watts
No abstract text is available yet for this article.
December 9, 2017: Lancet
https://www.readbyqxmd.com/read/29230215/potential-effects-of-horizontal-gene-exchange-in-the-human-gut
#18
Aaron Lerner, Torsten Matthias, Rustam Aminov
Many essential functions of the human body are dependent on the symbiotic microbiota, which is present at especially high numbers and diversity in the gut. This intricate host-microbe relationship is a result of the long-term coevolution between the two. While the inheritance of mutational changes in the host evolution is almost exclusively vertical, the main mechanism of bacterial evolution is horizontal gene exchange. The gut conditions, with stable temperature, continuous food supply, constant physicochemical conditions, extremely high concentration of microbial cells and phages, and plenty of opportunities for conjugation on the surfaces of food particles and host tissues, represent one of the most favorable ecological niches for horizontal gene exchange...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29207071/hepatocellular-carcinoma-targeted-nanoparticles-for-cancer-therapy
#19
Chien-Hsun Wu, Chun-Hsin Lan, Kuan-Lin Wu, Yao-Ming Wu, Wann-Neng Jane, Michael Hsiao, Han-Chung Wu
Nanocarriers, such as liposomes, have the potential to increase the payload of chemotherapeutic drugs while decreasing toxicity to non-target tissues; such advantageous properties can be further enhanced through surface conjugation of nanocarriers with targeting moieties. We previously reported that SP94 peptides, identified by phage display, exhibited higher binding affinity to human hepatocellular carcinoma (HCC) than to hepatocytes and other normal cells. Here, we confirm the tumor-targeting properties of SP94 peptide by near-infrared fluorescence imaging...
November 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29206153/is-genetic-mobilization-considered-when-using-bacteriophages-in-antimicrobial-therapy
#20
Lorena Rodríguez-Rubio, Joan Jofre, Maite Muniesa
The emergence of multi-drug resistant bacteria has undermined our capacity to control bacterial infectious diseases. Measures needed to tackle this problem include controlling the spread of antibiotic resistance, designing new antibiotics, and encouraging the use of alternative therapies. Phage therapy seems to be a feasible alternative to antibiotics, although there are still some concerns and legal issues to overcome before it can be implemented on a large scale. Here we highlight some of those concerns, especially those related to the ability of bacteriophages to transport bacterial DNA and, in particular, antibiotic resistance genes...
December 5, 2017: Antibiotics
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