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https://www.readbyqxmd.com/read/28096488/novel-superspreader-bacteriophages-promote-horizontal-gene-transfer-by-transformation
#1
Eric C Keen, Valery V Bliskovsky, Francisco Malagon, James D Baker, Jeffrey S Prince, James S Klaus, Sankar L Adhya
: Bacteriophages infect an estimated 10(23) to 10(25) bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). However, even though phage-plasmid interactions occur on a massive scale and have potentially significant evolutionary, ecological, and biomedical implications, plasmid fate upon phage infection and lysis has not been investigated to date. Here we show that a subset of the natural lytic phage population, which we dub "superspreaders," releases substantial amounts of intact, transformable plasmid DNA upon lysis, thereby promoting horizontal gene transfer by transformation...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096486/phage-derived-protein-induces-increased-platelet-activation-and-is-associated-with-mortality-in-patients-with-invasive-pneumococcal-disease
#2
Rahajeng N Tunjungputri, Fredrick M Mobegi, Amelieke J Cremers, Christa E van der Gaast-de Jongh, Gerben Ferwerda, Jacques F Meis, Nel Roeleveld, Stephen D Bentley, Alexander S Pastura, Sacha A F T van Hijum, Andre J van der Ven, Quirijn de Mast, Aldert Zomer, Marien I de Jonge
: To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated the association between the genotype of Streptococcus pneumoniae and disease outcomes for 349 bacteremic patients. A pneumococcal genome-wide association study (GWAS) demonstrated a strong correlation between 30-day mortality and the presence of the phage-derived gene pblB, encoding a platelet-binding protein whose effects on platelet activation were previously unknown. Platelets are increasingly recognized as key players of the innate immune system, and in sepsis, excessive platelet activation contributes to microvascular obstruction, tissue hypoperfusion, and finally multiorgan failure, leading to mortality...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28090795/isolation-and-characterization-of-anti-c-met-single-chain-fragment-variable-scfv-antibodies
#3
Elmira Safaie Qamsari, Zahra Sharifzadeh, Salman Bagheri, Farhad Riazi-Rad, Vahid Younesi, Mohsen Abolhassani, Sepideh Safaei Ghaderi, Behzad Baradaran, Mohammad Hossein Somi, Mehdi Yousefi
The receptor tyrosine kinase (RTK) Met is the cell surface receptor for hepatocyte growth factor (HGF) involved in invasive growth programs during embryogenesis and tumorgenesis. There is compelling evidence suggesting important roles for c-Met in colorectal cancer proliferation, migration, invasion, angiogenesis, and survival. Hence, a molecular inhibitor of an extracellular domain of c-Met receptor that blocks c-Met-cell surface interactions could be of great thera-peutic importance. In an attempt to develop molecular inhibitors of c-Met, single chain variable fragment (scFv) phage display libraries Tomlinson I + J against a specific synthetic oligopeptide from the extracellular domain of c-Met receptor were screened; selected scFv were then characterized using various immune techniques...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28090632/identification-of-highly-selective-mmp-14-inhibitory-fabs-by-deep-sequencing
#4
Tyler Lopez, Dong Hyun Nam, Evan Kaihara, Zahid Mustafa, Xin Ge
Matrix metalloproteinase (MMP)-14 is an important target for cancer treatment due to its critical roles in tumor invasion and metastasis. Previous failures of all compound-based broad-spectrum MMP inhibitors in clinical trials suggest that selectivity is the key for a successful therapy. With inherent high specificity, monoclonal antibodies (mAbs) therefore arise as attractive inhibitors able to target the particular MMP of interest. As a routine screening method, enzyme-linked immunosorbent assays (ELISA) have been applied to panned phage libraries for the isolation of mAbs inhibiting MMP-14...
January 16, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28076361/synergy-and-order-effects-of-antibiotics-and-phages-in-killing-pseudomonas-aeruginosa-biofilms
#5
Waqas Nasir Chaudhry, Jeniffer Concepción-Acevedo, Taehyun Park, Saadia Andleeb, James J Bull, Bruce R Levin
In contrast to planktonic cells, bacteria imbedded biofilms are notoriously refractory to treatment by antibiotics or bacteriophage (phage) used alone. Given that the mechanisms of killing differ profoundly between drugs and phages, an obvious question is whether killing is improved by combining antibiotic and phage therapy. However, this question has only recently begun to be explored. Here, in vitro biofilm populations of Pseudomonas aeruginosa PA14 were treated singly and with combinations of two phages and bactericidal antibiotics of five classes...
2017: PloS One
https://www.readbyqxmd.com/read/28064157/fviii-specific-human-chimeric-antigen-receptor-car-t-regulatory-cells-suppress-t-and-b-cell-responses-to-fviii
#6
Jeongheon Yoon, Anja Schmidt, Ai-Hong Zhang, Christoph Königs, Yong Chan Kim, David W Scott
Replacement therapy with factor VIII (FVIII) is used in hemophilia A patients for treatment of bleeding episodes or for prophylaxis. A common and serious problem with this therapy is the patient's immune response to FVIII, due to a lack of tolerance, leading to the formation of inhibitory antibodies. Development of tolerogenic therapies, other than standard ITI, is an unmet goal. We previously generated engineered antigen- specific regulatory T cells (Tregs), created by transduction of a recombinant T cell receptor (TCR) isolated from a hemophilia A subject's T cell clone...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28046082/the-phage-lysin-plyss2-decolonizes-streptococcus-suis-from-murine-intranasal-mucosa
#7
Daniel B Gilmer, Jonathan E Schmitz, Mya Thandar, Chad W Euler, Vincent A Fischetti
Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9...
2017: PloS One
https://www.readbyqxmd.com/read/28029647/peptide-guided-targeting-of-gpr55-for-anti-cancer-therapy
#8
Maria Mangini, Enrico Iaccino, Maria Giovanna Mosca, Selena Mimmi, Rosa D'Angelo, Ileana Quinto, Giuseppe Scala, Stefania Mariggiò
Expression of the lysophosphatidylinositol receptor GPR55 correlates with invasive potential of metastatic cells and bone metastasis formation of different types of tumors. These findings suggest a role for GPR55 signaling in cancer progression, including in lymphoproliferative diseases. Here, we screened a M13-phage-displayed random library using the bait of HEK293 cells that heterologously expressed full-length HA-GPR55. We selected a set of phagotopes that carried 7-mer insert peptides flanked by a pair of cysteine residues, which resulted in cyclized peptides...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28017694/pitfalls-to-avoid-when-using-phage-display-for-snake-toxins
#9
Andreas Hougaard Laustsen, Line Præst Lauridsen, Bruno Lomonte, Mikael Rørdam Andersen, Brian Lohse
Antivenoms against bites and stings from snakes, spiders, and scorpions are associated with immunological side effects and high cost of production, since these therapies are still derived from the serum of hyper-immunized production animals. Biotechnological innovations within envenoming therapies are thus warranted, and phage display technology may be a promising avenue for bringing antivenoms into the modern era of biologics. Although phage display technology represents a robust and high-throughput approach for the discovery of antibody-based antitoxins, several pitfalls may present themselves when animal toxins are used as targets for phage display selection...
December 23, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28007923/phages-fitness-virulence-and-synergy-a-novel-approach-for-the-therapy-of-infections-caused-by-pseudomonas-aeruginosa
#10
EDITORIAL
Charles W Stratton
No abstract text is available yet for this article.
December 22, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28007922/synergistic-interaction-between-phage-therapy-and-antibiotics-clears-pseudomonas-aeruginosa-infection-in-endocarditis-and-reduces-virulence
#11
Frank Oechslin, Philippe Piccardi, Stefano Mancini, Jérôme Gabard, Philippe Moreillon, José M Entenza, Gregory Resch, Yok-Ai Que
BACKGROUND: Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection. METHODS: In vitro fibrin-clots and rats with aortic EE were treated with an anti-pseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined...
December 22, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28006031/selection-and-characterization-of-tau-binding-%C3%A1-enantiomeric-peptides-with-potential-for-therapy-of-alzheimer-disease
#12
Christina Dammers, Deniz Yolcu, Laura Kukuk, Dieter Willbold, Marcus Pickhardt, Eckhard Mandelkow, Anselm H C Horn, Heinrich Sticht, Marwa Nidal Malhis, Nadja Will, Judith Schuster, Susanne Aileen Funke
A variety of neurodegenerative disorders, including Alzheimer disease (AD), are associated with neurofibrillary tangles composed of the tau protein, as well as toxic tau oligomers. Inhibitors of pathological tau aggregation, interrupting tau self-assembly, might be useful for the development of therapeutics. Employing mirror image phage display with a large peptide library (over 109 different peptides), we have identified tau fibril binding peptides consisting of d-enantiomeric amino acids. d-enantiomeric peptides are extremely protease stable and not or less immunogenic than l-peptides, and the suitability of d-peptides for in vivo applications have already been demonstrated...
2016: PloS One
https://www.readbyqxmd.com/read/28000755/the-balance-of-metagenomic-elements-shapes-the-skin-microbiome-in-acne-and-health
#13
Emma Barnard, Baochen Shi, Dezhi Kang, Noah Craft, Huiying Li
Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27984065/isolation-and-characterization-of-a-novel-human-scfv-inhibiting-egfr-viii-expressing-cancers
#14
Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Hassan Dariushnejad, Mohammad Kazem Hosseini
EGFRvIII, a mutant form of epidermal growth factor receptor is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. This tumor specific antigen has emerged as a promising candidate for antibody based therapy of several cancers. The aim of the present study was isolation and characterization of a human single chain antibody against EGFRvIII as a promising target for cancer therapy. For this, a synthetic peptide corresponding to EGFRvIII protein was used for screening the naive human scFv phage library...
October 29, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27978506/a-minireview-on-the-in-vitro-and-in-vivo-experiments-with-anti-escherichia-coli-o157-h7-phages-as-potential-biocontrol-and-phage-therapy-agents
#15
REVIEW
Salehe Sabouri, Zargham Sepehrizadeh, Sahar Amirpour-Rostami, Mikael Skurnik
Phage therapy is an old method of combating bacterial pathogens that has recently been taken into consideration due to the alarming spread of antibiotic resistance. Escherichia coli O157:H7 is a foodborne pathogen that causes hemorrhagic colitis and life-threatening Hemolytic Uremic Syndrome (HUS). There are several studies on isolation of specific phages against E. coli O157:H7 and more than 60 specific phages have been published so far. Although in vitro experiments have been successful in elimination or reduction of E...
December 11, 2016: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/27974392/phage-therapy-targeting-escherichia-coli-a-story-with-no-end
#16
Andrei Sorin Bolocan, Julie Callanan, Amanda Forde, Paul Ross, Colin Hill
Bacteriophages (phages) or bacterial viruses have long been proposed as an alternative therapy against antibiotic-resistant bacteria such as Escherichia coli Even though poorly documented in the scientific literature, a long clinical history of phage therapy in countries such as Russia and Georgia suggests potential value in the use of phages as antibacterial agents. Escherichia coli is responsible for a wide range of diseases, intestinal (diarrhoea) and extraintestinal (UTI, septicaemia, pneumoniae, meningitis), making it an ideal target for phage therapy...
November 2016: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/27966896/glioma-targeted-drug-delivery-enabled-by-a-multifunctional-peptide
#17
Mingfei Zhang, Xishan Chen, Man Ying, Jie Gao, Changyou Zhan, Weiyue Lu
The rapid proliferation of glioma relies on vigorous angiogenesis for the supply of essential nutrients; thus, a radical method of antiglioma therapy should include blocking tumor neovasculature formation. A phage display selected heptapeptide, the glioma-initiating cell peptide GICP, was previously reported as a ligand of VAV3 protein (a Rho GTPase guanine nucleotide exchange factor), which is overexpressed on glioma cells and tumor neovasculature. Therefore, GICP holds potential for the multifunctional targeting of glioma (tumor cells and neovasculature)...
December 14, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/27942361/isolation-characterization-and-antibacterial-activity-of-bacteriophages-against-methicillin-resistant-staphylococcus-aureus-in-pakistan
#18
Muhammad Hidayat Rasool, Rukhsana Yousaf, Abu Baker Siddique, Muhammad Saqalein, Mohsin Khurshid
BACKGROUND: In recent years, antibiotic resistance has been indicated as a paramount threat to public health. The use of bacteriophages appears to be a safer alternative for the control of bacterial infections. OBJECTIVES: The present study aims to explore sewage water for the presence of indigenous bacteriophages, and to investigate their antibacterial potential against Methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Bacterial isolates were first collected and identified from pus samples taken from the surgical and burn units using standard microbiological procedures...
October 2016: Jundishapur Journal of Microbiology
https://www.readbyqxmd.com/read/27934883/preclinical-evaluation-of-radiation-and-systemic-rgd-targeted-adeno-associated-virus-phage-tnf-gene-therapy-in-a-mouse-model-of-spontaneously-metastatic-melanoma
#19
T J Quinn, N Healy, A Sara, E Maggi, C S Claros, R Kabarriti, L Scandiuzzi, L Liu, J Gorecka, A Adem, I Basu, Z Yuan, C Guha
The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model...
December 9, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27932636/complete-genome-sequence-of-bacteriophage-ma12-which-infects-both-campylobacter-jejuni-and-salmonella-enterica-serovar-enteritidis
#20
Sunjin Lee, Taesoo Kwon, Su-Jin Chae, Jong-Hyun Kim, Yeon Ho Kang, Gyung Tae Chung, Dae-Won Kim, Deog-Yong Lee
Here, we announce the complete genome sequence of Salmonella enterica serovar Enteritidis (S Enteritidis) bacteriophage MA12, a 41-Kb chromosome. The strain can infect both Campylobacter jejuni (C. jejuni) and S Enteritidis and can be used in phage therapy experiments with poultry and poultry meat.
December 8, 2016: Genome Announcements
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