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https://www.readbyqxmd.com/read/28426329/mathematical-modelling-of-crispr-cas-system-effects-on-biofilm-formation
#1
Qasim Ali, Lindi M Wahl
Clustered regularly interspaced short palindromic repeats (CRISPR), linked with CRISPR associated (Cas) genes, can confer adaptive immunity to bacteria, against bacteriophage infections. Thus from a therapeutic standpoint, CRISPR immunity increases biofilm resistance to phage therapy. Recently, however, CRISPR-Cas genes have been implicated in reducing biofilm formation in lysogenized cells. Thus CRISPR immunity can have complex effects on phage-host-lysogen interactions, particularly in a biofilm. In this contribution, we develop and analyse a series of dynamical systems to elucidate and disentangle these interactions...
April 20, 2017: Journal of Biological Dynamics
https://www.readbyqxmd.com/read/28418081/assessment-of-biofilm-removal-capacity-of-a-broad-host-range-bacteriophage-jhp-against-pseudomonas-aeruginosa
#2
Muafia Shafique, Iqbal Ahmad Alvi, Zaigham Abbas, Shafiq Ur Rehman
Pseudomonas aeruginosa is an efficient biofilm-dwelling microbial pathogen, associated with nosocomial infections. These biofilm-associated infections are resistant to antibiotics and immune defenses, therefore pose major problem against their treatment. This scenario demands alternative therapeutic regimens, and bacteriophage therapy is one among potential strategies for clinical management of multiple drug resistance. In this investigation, the efficacy of a bacteriophage, JHP, is evaluated to eradicate P...
April 18, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28407482/salmonella-typhimurium-diarrhea-reveals-basic-principles-of-enteropathogen-infection-and-disease-promoted-dna-exchange
#3
REVIEW
Sandra Y Wotzka, Bidong D Nguyen, Wolf-Dietrich Hardt
Despite decades of research, efficient therapies for most enteropathogenic bacteria are still lacking. In this review, we focus on Salmonella enterica Typhimurium (S. Typhimurium), a frequent cause of acute, self-limiting food-borne diarrhea and a model that has revealed key principles of enteropathogen infection. We review the steps of gut infection and the mucosal innate-immune defenses limiting pathogen burdens, and we discuss how inflammation boosts gut luminal S. Typhimurium growth. We also discuss how S...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28405193/the-efficacy-of-isolated-bacteriophages-from-pig-farms-against-esbl-ampc-producing-escherichia-coli-from-pig-and-turkey-farms
#4
Aneta Skaradzińska, Paulina Śliwka, Marta Kuźmińska-Bajor, Grzegorz Skaradziński, Anna Rząsa, Anika Friese, Nicole Roschanski, Jayaseelan Murugaiyan, Uwe H Roesler
Extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases are plasmid (but also chromosomally) encoded enzymes found in Enterobacteriaceae, determining resistance to a variety of important antibiotics including penicillins, cephalosporins, and monobactams. In recent decades, the prevalence of ESBL/AmpC-producing bacteria has increased rapidly across the world. Here, we evaluate the potential use of bacteriophages in terms of a reduction of antibiotic-resistant bacteria in healthy animals. The aim of our studies was to isolate bacteriophages capable of destroying ESBL/AmpC-producing Escherichia coli isolated from livestock habitats...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28388565/prokaryotic-expression-of-mlaa-34-and-generation-of-a-novel-human-scfv-against-mlaa-34-by-phage-display-technology
#5
Yang Zhang, Pengyu Zhang, Aili He, Yun Yang, Jianli Wang, Hui Zhang, Wanggang Zhang
MLAA-34 is a newly identified monocytic leukemia-associated antigen that is overexpressed in acute monocytic leukemia specifically, thus providing a novel target for the therapy of acute monocytic leukemia. In this study, we first expressed MLAA-34 protein in Escherichia coli (E.coli) BL21 (DE3) cells and purified it by nickel ion affinity chromatography with high purity (>90%). Then, MLAA-34 was used as antigen for biopanning anti-MLAA-34 single chain antibody fragment (ScFv) from a fully human ScFv library, and a high affinity ScFv named MA1 was selected by phage-ELISA...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386250/means-to-facilitate-the-overcoming-of-gastric-juice-barrier-by-a-therapeutic-staphylococcal-bacteriophage-a5-80
#6
Ryszard Międzybrodzki, Marlena Kłak, Ewa Jończyk-Matysiak, Barbara Bubak, Anna Wójcik, Marta Kaszowska, Beata Weber-Dąbrowska, Małgorzata Łobocka, Andrzej Górski
In this article we compare the efficacy of different pharmacological agents (ranitidine, and omeprazole) to support phage transit from stomach to distal portions of the gastrointestinal tract in rats. We show that a temporal modification of environment in the animal stomach may protect Twort-like therapeutic antistaphylococcal phage A5/80 (from bacteriophage collection of the Hirszfeld Institute of Immunology and Experimental Therapy PAS in Wroclaw, Poland) from the inactivation by gastric juice effectively enough to enable a significant fraction of orally administered A5/80 to pass to the intestine...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28377527/phage-inhibit-pathogen-dissemination-by-targeting-bacterial-migrants-in-a-chronic-infection-model
#7
Sophie E Darch, Kasper N Kragh, Evelyn A Abbott, Thomas Bjarnsholt, James J Bull, Marvin Whiteley
The microbial communities inhabiting chronic infections are often composed of spatially organized micrometer-sized, highly dense aggregates. It has recently been hypothesized that aggregates are responsible for the high tolerance of chronic infections to host immune functions and antimicrobial therapies. Little is currently known regarding the mechanisms controlling aggregate formation and antimicrobial tolerance primarily because of the lack of robust, biologically relevant experimental systems that promote natural aggregate formation...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28375731/crispr-cas9-structures-and-mechanisms
#8
Fuguo Jiang, Jennifer A Doudna
Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems employ the dual RNA-guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific double-stranded breaks in target DNA. Target recognition strictly requires the presence of a short protospacer adjacent motif (PAM) flanking the target site, and subsequent R-loop formation and strand scission are driven by complementary base pairing between the guide RNA and target DNA, Cas9-DNA interactions, and associated conformational changes...
March 30, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28369562/resistance-gene-transfer-induction-of-transducing-phage-by-sub-inhibitory-concentrations-of-antimicrobials-is-not-correlated-to-induction-of-lytic-phage
#9
Kinga I Stanczak-Mrozek, Ken G Laing, Jodi A Lindsay
Objectives: Horizontal gene transfer of antimicrobial resistance (AMR) genes between clinical isolates via transduction is poorly understood. MRSA are opportunistic pathogens resistant to all classes of antimicrobial agents but currently no strains are fully drug resistant. AMR gene transfer between Staphylococcus aureus isolates is predominantly due to generalized transduction via endogenous bacteriophage, and recent studies have suggested transfer is elevated during host colonization...
March 20, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28359814/targeted-delivery-of-anticancer-drugs-to-tumor-vessels-by-use-of-liposomes-modified-with-a-peptide-identified-by-phage-biopanning-with-human-endothelial-progenitor-cells
#10
Tatsuya Fukuta, Tomohiro Asai, Yuri Kiyokawa, Takashi Nakada, Koji Bessyo-Hirashima, Natsuki Fukaya, Kenji Hyodo, Kazuma Takase, Hiroshi Kikuchi, Naoto Oku
As tumor angiogenic vessels are critical for tumor growth and express different molecules on their surface from those on normal vessels, these vessels are expected to be an ideal target for anticancer drug delivery systems. It was previously reported that endothelial progenitor cells (EPCs) are involved in angiogenesis, tumor growth, and metastasis, and that EPCs show gene expression patterns similar to those of tumor endothelial cells. In the present study, a tumor vessel-targeting peptide, ASSHN, was identified from a phage-display peptide library by in vitro biopanning with human EPCs (hEPCs) and in vivo biopanning using angiogenesis model mice prepared by the dorsal air sac method...
March 27, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28356444/antibody-mediated-inhibition-of-tspan12-ameliorates-vasoproliferative-retinopathy-through-suppression-of-%C3%AE-catenin-signaling
#11
Felicitas Bucher, Ding Zhang, Edith Aguilar, Susumu Sakimoto, Sophia Diaz-Aguilar, Mauricio Rosenfeld, Zhao Zha, Hongkai Zhang, Martin Friedlander, Kyungmoo Yea
Background -Anti-angiogenic biologicals represent an important concept for the treatment of vasoproliferative diseases. However, the need for continued treatment, the presence of non-responders and the risk of long-term side-effects limit the success of existing therapeutic agents. While Tspan12 has been shown to regulate retinal vascular development, nothing is known about its involvement in neovascular disease and its potential as novel therapeutic target for the treatment of vasoproliferative diseases. Methods -Rodent models of retinal neovascular disease including the mouse model of oxygen-induced retinopathy (OIR) and the very low density lipoprotein receptor (VLDLR) knockout (KO) mouse model were analyzed for Tspan/β-catenin regulation...
March 29, 2017: Circulation
https://www.readbyqxmd.com/read/28353419/a-new-anti-mesothelin-antibody-targets-selectively-the-membrane-associated-form
#12
Kamal Asgarov, Jeremy Balland, Charline Tirole, Adeline Bouard, Virginie Mougey, Diana Ramos, António Barroso, Vincent Zangiacomi, Marine Jary, Stefano Kim, Maria Gonzalez-Pajuelo, Bernard Royer, Hans de Haard, Andy Clark, John Wijdenes, Christophe Borg
Mesothelin is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that shows promise as a target for antibody-directed cancer therapy. High levels of soluble forms of the antigen represent a barrier to directing therapy to cellular targets. The ability to develop antibodies that can selectively discriminate between membrane-bound and soluble conformations of a specific protein, and thus target only the membrane-associated antigen, is a substantive issue. We show that use of a tolerance protocol provides a route to such discrimination...
April 2017: MAbs
https://www.readbyqxmd.com/read/28335451/a-review-of-phage-therapy-against-bacterial-pathogens-of-aquatic-and-terrestrial-organisms
#13
REVIEW
Janis Doss, Kayla Culbertson, Delilah Hahn, Joanna Camacho, Nazir Barekzi
Since the discovery of bacteriophage in the early 1900s, there have been numerous attempts to exploit their innate ability to kill bacteria. The purpose of this report is to review current findings and new developments in phage therapy with an emphasis on bacterial diseases of marine organisms, humans, and plants. The body of evidence includes data from studies investigating bacteriophage in marine and land environments as modern antimicrobial agents against harmful bacteria. The goal of this paper is to present an overview of the topic of phage therapy, the use of phage-derived protein therapy, and the hosts that bacteriophage are currently being used against, with an emphasis on the uses of bacteriophage against marine, human, animal and plant pathogens...
March 18, 2017: Viruses
https://www.readbyqxmd.com/read/28329379/the-lysis-of-pathogenic-escherichia-coli-by-bacteriophages-releases-less-endotoxin-than-betalactams
#14
Nicolas Dufour, Raphaëlle Delattre, Jean-Damien Ricard, Laurent Debarbieux
Background: Beside numerous experimental data assessing phage therapy efficacy, questions regarding safety of this approach are not sufficiently addressed. In particular, as phages can kill bacterial cells within less than 10 minutes, the associated endotoxin release (ER) in severe infections caused by Gram-negative bacteria could be a matter of concern. Methods: Two therapeutic virulent phages and four reference antibiotics were studied in vitro for their ability to kill two pathogenic strains of Escherichia coli and generate an ER...
March 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28329182/phage-therapy-considerations-and-challenges-for-development
#15
Rebecca Reindel, Cara R Fiore
No abstract text is available yet for this article.
March 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28302013/multicyclic-peptides-as-scaffolds-for-the-development-of-tumor-targeting-agents
#16
Anastasia Loktev, Uwe Haberkorn, Walter Mier
The lack of specificity of traditional cytotoxic drugs triggers the development of anticancer agents with high selectivity to tumor-specific proteins. The unveiling of target structures such as EGFR or Her2 allows the focused development of novel therapies and has strongly advanced tumor treatment. Tumor-specific high-affinity ligands can be identified by using display techniques such as phage, yeast surface, ribosome and mRNA display. These techniques enable the screening of huge libraries, consequently providing a valuable alternative to rational drug development...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28299517/characterization-and-complete-genome-sequence-analysis-of-a-novel-virulent-siphoviridae-phage-against-staphylococcus-aureus-isolated-from-bovine-mastitis-in-xinjiang-china
#17
Qian Zhang, Shaozhen Xing, Qiang Sun, Guangqian Pei, Shi Cheng, Yannan Liu, Xiaoping An, Xianglilan Zhang, Yonggang Qu, Yigang Tong
Bovine mastitis is one of the most costly diseases in dairy cows worldwide. It can be caused by over 150 different microorganisms, where Staphylococcus aureus is the most frequently isolated and a major pathogen responsible for heavy economic losses in dairy industry. Although antibiotic therapy is most widely used, alternative treatments are necessary due to the increasing antibiotic resistance. Using phage for pathogen control is a promising tool in the fight against antibiotic resistance. Mainly using high-throughput sequencing, bioinformatics and our proposed phage termini identification method, we have isolated and characterized a novel virulent phage, designated as vB_SauS_IMEP5, from manure collected from dairy farms in Shihezi, Xinjiang, China, for use as a biocontrol agent against Staphylococcus aureus infections...
March 15, 2017: Virus Genes
https://www.readbyqxmd.com/read/28291834/the-isolation-and-characterization-of-stenotrophomonas-maltophilia-t4-like-bacteriophage-dlp6
#18
Danielle L Peters, Paul Stothard, Jonathan J Dennis
Increasing isolation of the extremely antibiotic resistant bacterium Stenotrophomonas maltophilia has caused alarm worldwide due to the limited treatment options available. A potential treatment option for fighting this bacterium is 'phage therapy', the clinical application of bacteriophages to selectively kill bacteria. Bacteriophage DLP6 (vB_SmoM-DLP6) was isolated from a soil sample using clinical isolate S. maltophilia strain D1571 as host. Host range analysis of phage DLP6 against 27 clinical S. maltophilia isolates shows successful infection and lysis in 13 of the 27 isolates tested...
2017: PloS One
https://www.readbyqxmd.com/read/28289407/a-novel-antimicrobial-endolysin-lyspa26-against-pseudomonas-aeruginosa
#19
Mingquan Guo, Chunyan Feng, Jie Ren, Xuran Zhuang, Yan Zhang, Yongzhang Zhu, Ke Dong, Ping He, Xiaokui Guo, Jinhong Qin
The global increase in multidrug resistant (MDR) bacteria has led to phage therapy being refocused upon. A novel endolysin, LysPA26, containing a lysozyme-like domain, was screened against Pseudomonas aeruginosa in this study. It had activity against MDR P. aeruginosa without pretreatment with an outer-membrane permeabilizer. LysPA26 could kill up to 4 log units P. aeruginosa in 30 min. In addition, temperature and pH effect assays revealed that LysPA26 had good stability over a broad range of pH and temperatures...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28286740/long-term-safety-of-topical-bacteriophage-application-to-the-frontal-sinus-region
#20
Amanda J Drilling, Mian L Ooi, Dijana Miljkovic, Craig James, Peter Speck, Sarah Vreugde, Jason Clark, Peter-John Wormald
Background:Staphylococcus aureus biofilms contribute negatively to a number of chronic conditions, including chronic rhinosinusitis (CRS). With the inherent tolerance of biofilm-bound bacteria to antibiotics and the global problem of bacterial antibiotic resistance, the need to develop novel therapeutics is paramount. Phage therapy has previously shown promise in treating sinonasal S. aureus biofilms. Methods: This study investigates the long term (20 days) safety of topical sinonasal flushes with bacteriophage suspensions...
2017: Frontiers in Cellular and Infection Microbiology
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