Artículos de revistas: "Phage filamenteux"

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Souriau, C., The Duc Hua, MP Lefranc y M. Weill. "Présentation a la surface de phages filamenteux : les multiples applications du phage display." médecine/sciences 14, n.º 3 (1998): 300. http://dx.doi.org/10.4267/10608/1033.

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Faruque, Shah M., Iftekhar Bin Naser, Kazutaka Fujihara, Pornphan Diraphat, Nityananda Chowdhury, M. Kamruzzaman, Firdausi Qadri, Shinji Yamasaki, A. N. Ghosh y John J. Mekalanos. "Genomic Sequence and Receptor for the Vibrio cholerae Phage KSF-1Φ: Evolutionary Divergence among Filamentous Vibriophages Mediating Lateral Gene Transfer". Journal of Bacteriology 187, n.º 12 (15 de junio de 2005): 4095–103. http://dx.doi.org/10.1128/jb.187.12.4095-4103.2005.

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ABSTRACT KSF-1Φ, a novel filamentous phage of Vibrio cholerae, supports morphogenesis of the RS1 satellite phage by heterologous DNA packaging and facilitates horizontal gene transfer. We analyzed the genomic sequence, morphology, and receptor for KSF-1Φ infection, as well as its phylogenetic relationships with other filamentous vibriophages. While strains carrying the mshA gene encoding mannose-sensitive hemagglutinin (MSHA) type IV pilus were susceptible to KSF-1Φ infection, naturally occurring MSHA-negative strains and an mshA deletion mutant were resistant. Furthermore, d-mannose as well as a monoclonal antibody against MSHA inhibited infection of MSHA-positive strains by the phage, suggesting that MSHA is the receptor for KSF-1Φ. The phage genome comprises 7,107 nucleotides, containing 14 open reading frames, 4 of which have predicted protein products homologous to those of other filamentous phages. Although the overall genetic organization of filamentous phages appears to be preserved in KSF-1Φ, the genomic sequence of the phage does not have a high level of identity with that of other filamentous phages and reveals a highly mosaic structure. Separate phylogenetic analysis of genomic sequences encoding putative replication proteins, receptor-binding proteins, and Zot-like proteins of 10 different filamentous vibriophages showed different results, suggesting that the evolution of these phages involved extensive horizontal exchange of genetic material. Filamentous phages which use type IV pili as receptors were found to belong to different branches. While one of these branches is represented by CTXΦ, which uses the toxin-coregulated pilus as its receptor, at least four evolutionarily diverged phages share a common receptor MSHA, and most of these phages mediate horizontal gene transfer. Since MSHA is present in a wide variety of V. cholerae strains and is presumed to express in the environment, diverse filamentous phages using this receptor are likely to contribute significantly to V. cholerae evolution.

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Chibani, Cynthia Maria, Robert Hertel, Michael Hoppert, Heiko Liesegang y Carolin Charlotte Wendling. "Closely Related Vibrio alginolyticus Strains Encode an Identical Repertoire of Caudovirales-Like Regions and Filamentous Phages". Viruses 12, n.º 12 (27 de noviembre de 2020): 1359. http://dx.doi.org/10.3390/v12121359.

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Many filamentous vibriophages encode virulence genes that lead to the emergence of pathogenic bacteria. Most genomes of filamentous vibriophages characterized up until today were isolated from human pathogens. Despite genome-based predictions that environmental Vibrios also contain filamentous phages that contribute to bacterial virulence, empirical evidence is scarce. This study aimed to characterize the bacteriophages of a marine pathogen, Vibrio alginolyticus (Kiel-alginolyticus ecotype) and to determine their role in bacterial virulence. To do so, we sequenced the phage-containing supernatant of eight different V. alginolyticus strains, characterized the phages therein and performed infection experiments on juvenile pipefish to assess their contribution to bacterial virulence. We were able to identify two actively replicating filamentous phages. Unique to this study was that all eight bacteria of the Kiel-alginolyticus ecotype have identical bacteriophages, supporting our previously established theory of a clonal expansion of the Kiel-alginolyticus ecotype. We further found that in one of the two filamentous phages, two phage-morphogenesis proteins (Zot and Ace) share high sequence similarity with putative toxins encoded on the Vibrio cholerae phage CTXΦ. The coverage of this filamentous phage correlated positively with virulence (measured in controlled infection experiments on the eukaryotic host), suggesting that this phage contributes to bacterial virulence.

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Campos, Javier, Eriel Martínez, Edith Suzarte, Boris L. Rodríguez, Karen Marrero, Yussuan Silva, Talena Ledón, Ricardo del Sol y Rafael Fando. "VGJφ, a Novel Filamentous Phage of Vibrio cholerae, Integrates into the Same Chromosomal Site as CTXφ". Journal of Bacteriology 185, n.º 19 (1 de octubre de 2003): 5685–96. http://dx.doi.org/10.1128/jb.185.19.5685-5696.2003.

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ABSTRACT We describe a novel filamentous phage, designated VGJφ, isolated from strain SG25-1 of Vibrio cholerae O139, which infects all O1 (classical and El Tor) and O139 strains tested. The sequence of the 7,542 nucleotides of the phage genome reveals that VGJφ has a distinctive region of 775 nucleotides and a conserved region with an overall genomic organization similar to that of previously characterized filamentous phages, such as CTXφ of V. cholerae and Ff phages of Escherichia coli. The conserved region carries 10 open reading frames (ORFs) coding for products homologous to previously reported peptides of other filamentous phages, and the distinctive region carries one ORF whose product is not homologous to any known peptide. VGJφ, like other filamentous phages, uses a type IV pilus to infect V. cholerae; in this case, the pilus is the mannose-sensitive hemagglutinin. VGJφ-infected V. cholerae overexpresses the product of one ORF of the phage (ORF112), which is similar to single-stranded DNA binding proteins of other filamentous phages. Once inside a cell, VGJφ is able to integrate its genome into the same chromosomal attB site as CTXφ, entering into a lysogenic state. Additionally, we found an attP structure in VGJφ, which is also conserved in several lysogenic filamentous phages from different bacterial hosts. Finally, since different filamentous phages seem to integrate into the bacterial dif locus by a general mechanism, we propose a model in which repeated integration events with different phages might have contributed to the evolution of the CTX chromosomal region in V. cholerae El Tor.

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Chopin, Marie-Christine, Annette Rouault, S. Dusko Ehrlich y Michel Gautier. "Filamentous Phage Active on the Gram-Positive Bacterium Propionibacterium freudenreichii". Journal of Bacteriology 184, n.º 7 (1 de abril de 2002): 2030–33. http://dx.doi.org/10.1128/jb.184.7.2030-2033.2002.

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ABSTRACT We present the first description of a single-stranded DNA filamentous phage able to replicate in a gram-positive bacterium. Phage B5 infects Propionibacterium freudenreichii and has a genome consisting of 5,806 bases coding for 10 putative open reading frames. The organization of the genome is very similar to the organization of the genomes of filamentous phages active on gram-negative bacteria. The putative coat protein exhibits homology with the coat proteins of phages PH75 and Pf3 active on Thermus thermophilus and Pseudomonas aeruginosa, respectively. B5 is, therefore, evolutionarily related to the filamentous phages active on gram-negative bacteria.

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Lin, Nien-Tsung, Tzu-Jun Liu, Tze-Ching Lee, Bih-Yuh You, Ming-Haw Yang, Fu-Shyan Wen y Yi-Hsiung Tseng. "The Adsorption Protein Genes of Xanthomonas campestris Filamentous Phages Determining Host Specificity". Journal of Bacteriology 181, n.º 8 (15 de abril de 1999): 2465–71. http://dx.doi.org/10.1128/jb.181.8.2465-2471.1999.

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ABSTRACT Gene III (gIII) of φLf, a filamentous phage specifically infecting Xanthomonas campestris pv. campestris, was previously shown to encode a virion-associated protein (pIII) required for phage adsorption. In this study, the transcription start site for the gene and the N-terminal sequence of the protein were determined, resulting in the revision of the translation initiation site from the one previously predicted for this gene. For comparative study, the gIII of φXv, a filamentous phage specifically infecting X. campestris pv. vesicatoria, was cloned and sequenced. The deduced amino acid sequences of these two pIIIs exhibit a high degree of identity in their C-terminal halves and possess the structural features typical of the adsorption proteins of filamentous phages: a signal sequence in the N terminus, a long glycine-rich region near the center, and a hydrophobic membrane anchorage domain in the C terminus. The regions between gIII and the upstreamgVIII, 128 nucleotides in both phages, are larger than those of other filamentous phages. A hybrid phage of φXv, consisting of the φLf pIII and all the other components derived from φXv, was able to infect X. campestris pv. campestris but notX. campestris pv. vesicatoria, indicating thatgIII is the gene specifying host specificity and demonstrating the interchangeability of the pIIIs.

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7

Barbas, S. M. y C. F. Barbas. "Filamentous phage display". Fibrinolysis 8 (enero de 1994): 245–52. http://dx.doi.org/10.1016/0268-9499(94)90722-6.

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8

Goehlich, Henry, Olivia Roth y Carolin C. Wendling. "Filamentous phages reduce bacterial growth in low salinities". Royal Society Open Science 6, n.º 12 (diciembre de 2019): 191669. http://dx.doi.org/10.1098/rsos.191669.

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Being non-lytic, filamentous phages can replicate at high frequencies and often carry virulence factors, which are important in the evolution and emergence of novel pathogens. However, their net effect on bacterial fitness remains unknown. To understand the ecology and evolution between filamentous phages and their hosts, it is important to assess (i) fitness effects of filamentous phages on their hosts and (ii) how these effects depend on the environment. To determine how the net effect on bacterial fitness by filamentous phages changes across environments, we constructed phage–bacteria infection networks at ambient 15 practical salinity units (PSU) and stressful salinities (11 and 7 PSU) using the marine bacterium, Vibrio alginolyticus and its derived filamentous phages as model system. We observed no significant difference in network structure at 15 and 11 PSU. However, at 7 PSU phages significantly reduced bacterial growth changing network structure. This pattern was mainly driven by a significant increase in bacterial susceptibility. Our findings suggest that filamentous phages decrease bacterial growth, an indirect measure of fitness in stressful environmental conditions, which might impact bacterial communities, alter horizontal gene transfer events and possibly favour the emergence of novel pathogens in environmental Vibrios .

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9

Campos, Javier, Eriel Martínez, Yovanny Izquierdo y Rafael Fando. "VEJφ, a novel filamentous phage of Vibrio cholerae able to transduce the cholera toxin genes". Microbiology 156, n.º 1 (1 de enero de 2010): 108–15. http://dx.doi.org/10.1099/mic.0.032235-0.

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A novel filamentous bacteriophage, designated VEJφ, was isolated from strain MO45 of Vibrio cholerae of the O139 serogroup. A molecular characterization of the phage was carried out, which included sequencing of its whole genome, study of the genomic structure, identification of the phage receptor, and determination of the function of some of the genes, such as those encoding the major capsid protein and the single-stranded DNA-binding protein. The genome nucleotide sequence of VEJφ, which consists of 6842 bp, revealed that it is organized in modules of functionally related genes in an array that is characteristic of the genus Inovirus (filamentous phages). VEJφ is closely related to other previously described filamentous phages of V. cholerae, including VGJφ, VSK and fs1. Like these phages, VEJφ uses as a cellular receptor the type IV fimbria called the mannose-sensitive haemagglutinin (MSHA). It was also demonstrated that VEJφ, like phage VGJφ, is able to transmit the genome of phage CTXφ, and therefore the genes encoding the cholera toxin (CT), horizontally among populations of V. cholerae expressing the MSHA receptor fimbria. This suggests that the variety of phages implicated in the horizontal transmission of the CT genes could be more diverse than formerly thought.

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Cairns, Johannes, Sebastián Coloma, Kaarina Sivonen y Teppo Hiltunen. "Evolving interactions between diazotrophic cyanobacterium and phage mediate nitrogen release and host competitive ability". Royal Society Open Science 3, n.º 12 (diciembre de 2016): 160839. http://dx.doi.org/10.1098/rsos.160839.

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Interactions between nitrogen-fixing (i.e. diazotrophic) cyanobacteria and their viruses, cyanophages, can have large-scale ecosystem effects. These effects are mediated by temporal alterations in nutrient availability in aquatic systems owing to the release of nitrogen and carbon sources from cells lysed by phages, as well as by ecologically important changes in the diversity and fitness of cyanobacterial populations that evolve in the presence of phages. However, ecological and evolutionary feedbacks between phages and nitrogen-fixing cyanobacteria are still relative poorly understood. Here, we used an experimental evolution approach to test the effect of interactions between a common filamentous, nitrogen-fixing cyanobacterium ( Nodularia sp.) and its phage on cellular nitrogen release and host properties. Ecological, community-level effects of phage-mediated nitrogen release were tested with a phytoplankton bioassay. We found that cyanobacterial nitrogen release increased significantly as a result of viral lysis, which was associated with enhanced growth of phytoplankton species in cell-free filtrates compared with phage-resistant host controls in which lysis and subsequent nutrient release did not occur after phage exposure. We also observed an ecologically important change among phage-evolved cyanobacteria with phage-resistant phenotypes, a short-filamentous morphotype with reduced buoyancy compared with the ancestral long-filamentous morphotype. Reduced buoyancy might decrease the ability of these morphotypes to compete for light compared with longer, more buoyant filaments. Together, these findings demonstrate the potential of cyanobacteria–phage interactions to affect ecosystem biogeochemical cycles and planktonic community dynamics.

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Xue, Hong, Yan Xu, Yan Boucher y Martin F. Polz. "High Frequency of a Novel Filamentous Phage, VCYϕ, within an Environmental Vibrio cholerae Population". Applied and Environmental Microbiology 78, n.º 1 (21 de octubre de 2011): 28–33. http://dx.doi.org/10.1128/aem.06297-11.

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ABSTRACTEnvironmentalVibrio choleraestrains isolated from a coastal brackish pond (Oyster Pond, Woods Hole, MA) carried a novel filamentous phage, VCYϕ, which can exist as a host genome integrative form (IF) and a plasmid-like replicative form (RF). Outside the cell, the phage displays a morphology typical ofInovirus, with filamentous particles ∼1.8 μm in length and 7 nm in width. Four independent RF isolates had identical genomes, except for 8 single nucleotide polymorphisms clustered in two regions. The overall genome size is 7,103 bp with 11 putative open reading frames organized into three functional modules (replication, structure and assembly, and regulation). VCYϕ shares sequence similarity with other filamentous phages (including cholera disease-associated CTX) in a highly mosaic manner, indicating evolution by horizontal gene transfer and recombination. VCYϕ integrates in the vicinity of the putative translation initiation factor Sui1 in chromosome II ofV. cholerae. A screen of 531 closely related host isolates showed that ∼40% harbored phages, with 27% and 13% carrying the IF and RF, respectively. The relative frequencies of the RF and IF differed among strains isolated from the pond or lagoon of Oyster Pond, suggesting that the host habitat influences intracellular phage biology. The overall high prevalence within the host population shows that filamentous phages can be an important component of the environmental biology ofV. cholerae.

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Ding, Yan-Li, Mei-Yun Liu, Wei Han, Sheng-Li Yang, Hui Liu y Yi Gong. "Application of Phage-displayed Single Chain Antibodies in Western Blot". Acta Biochimica et Biophysica Sinica 37, n.º 3 (1 de marzo de 2005): 205–9. http://dx.doi.org/10.1093/abbs/37.3.205.

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Abstract A phage display single chain fragment variable library constructed on pIII protein of M13 filamentous phage was screened using B-lymphocyte stimulator and FP248 as selective molecules. After four rounds of panning, there was a remarkable enrichment in the titer of bound phages. Twenty phage clones were selected from the last round and screened by means of phage-ELISA. With the antibody phages as primary antibodies in Western blot, we developed a method for detecting the specific antigen. The dilutions of antibody phages depend on the affinity between antibody-displayed phage particles and antigens.

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Chang, Bin, Hatsumi Taniguchi, Hiroshi Miyamoto y Shin-ichi Yoshida. "Filamentous Bacteriophages of Vibrio parahaemolyticus as a Possible Clue to Genetic Transmission". Journal of Bacteriology 180, n.º 19 (1 de octubre de 1998): 5094–101. http://dx.doi.org/10.1128/jb.180.19.5094-5101.1998.

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ABSTRACT We have previously reported the isolation and characterization of two filamentous bacteriophages of Vibrio parahaemolyticus, designated Vf12 and Vf33. In this study, to understand the potential of these phages as tools for genetic transmission, we investigated the gene structures of replicative-form (RF) DNAs of their genomes and the distribution of these DNAs on chromosomal and extrachromosomal DNAs. The 7,965-bp nucleotide sequences of Vf12 and Vf33 were determined. An analysis of the overall gene structures revealed that Vf12 and Vf33 had conserved regions and distinctive regions. The gene organization of their conserved regions was similar to that of CTX phage ofVibrio cholerae and coliphage Ff of Escherichia coli, while their distinctive regions were characteristic of Vf12 and Vf33 phage genomes. Southern blot hybridization testing revealed that the filamentous phage genomes integrated into chromosomal DNA ofV. parahaemolyticus at the distinctive region of the phage genome and were also distributed on some plasmids ofV. parahaemolyticus and total cellular DNAs of oneVibrio damsela and one nonagglutinable Vibriostrain tested. These results strongly suggest the possibilities of genetic interaction among the bacteriophage Vf12 and Vf33 genomes and chromosomal and plasmid-borne DNAs of V. parahaemolyticus strains and of genetic transmission among strains through these filamentous phages.

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Nakamura, Michihiro, Kouhei Tsumoto, Izumi Kumagai y Kazunori Ishimura. "A morphologic study of filamentous phage infection ofEscherichia coliusing biotinylated phages". FEBS Letters 536, n.º 1-3 (22 de enero de 2003): 167–72. http://dx.doi.org/10.1016/s0014-5793(03)00050-4.

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Chen, Qingquan, Tejas Dharmaraj, Pamela C. Cai, Elizabeth B. Burgener, Naomi L. Haddock, Andy J. Spakowitz y Paul L. Bollyky. "Bacteriophage and Bacterial Susceptibility, Resistance, and Tolerance to Antibiotics". Pharmaceutics 14, n.º 7 (7 de julio de 2022): 1425. http://dx.doi.org/10.3390/pharmaceutics14071425.

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Bacteriophages, viruses that infect and replicate within bacteria, impact bacterial responses to antibiotics in complex ways. Recent studies using lytic bacteriophages to treat bacterial infections (phage therapy) demonstrate that phages can promote susceptibility to chemical antibiotics and that phage/antibiotic synergy is possible. However, both lytic and lysogenic bacteriophages can contribute to antimicrobial resistance. In particular, some phages mediate the horizontal transfer of antibiotic resistance genes between bacteria via transduction and other mechanisms. In addition, chronic infection filamentous phages can promote antimicrobial tolerance, the ability of bacteria to persist in the face of antibiotics. In particular, filamentous phages serve as structural elements in bacterial biofilms and prevent the penetration of antibiotics. Over time, these contributions to antibiotic tolerance favor the selection of resistance clones. Here, we review recent insights into bacteriophage contributions to antibiotic susceptibility, resistance, and tolerance. We discuss the mechanisms involved in these effects and address their impact on bacterial fitness.

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Karlsson, Fredrik, Ann-Christin Malmborg-Hager, Ann-Sofie Albrekt y Carl A. K. Borrebaeck. "Genome-wide comparison of phage M13-infected vs. uninfectedEscherichia coli". Canadian Journal of Microbiology 51, n.º 1 (1 de enero de 2005): 29–35. http://dx.doi.org/10.1139/w04-113.

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To identify Escherichia coli genes potentially regulated by filamentous phage infection, we used oligonucleotide microarrays. Genome-wide comparison of phage M13-infected and uninfected E. coli, 2 and 20 min after infection, was performed. The analysis revealed altered transcription levels of 12 E. coli genes in response to phage infection, and the observed regulation of phage genes correlated with the known in vivo pattern of M13 mRNA species. Ten of the 12 host genes affected could be grouped into 3 different categories based on cellular function, suggesting a coordinated response. The significantly upregulated genes encode proteins involved in reactions of the energy-generating phosphotransferase system and transcription processing, which could be related to phage transcription. No genes belonging to any known E. coli stress response pathways were scored as upregulated. Furthermore, phage infection led to significant downregulation of transcripts of the bacterial genes gadA, gadB, hdeA, gadE, slp, and crl. These downregulated genes are normally part of the host stress response mechanisms that protect the bacterium during conditions of acid stress and stationary phase transition. The phage-infected cells demonstrated impaired function of the oxidative and the glutamate-dependent acid resistance systems. Thus, global transcriptional analysis and functional analysis revealed previously unknown host responses to filamentous phage infection.Key words: filamentous phage infection, global transcriptional analysis, AR, Escherichia coli.

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17

Akremi, Ismahen, Dominique Holtappels, Wided Brabra, Mouna Jlidi, Adel Hadj Ibrahim, Manel Ben Ali, Kiandro Fortuna et al. "First Report of Filamentous Phages Isolated from Tunisian Orchards to Control Erwinia amylovora". Microorganisms 8, n.º 11 (10 de noviembre de 2020): 1762. http://dx.doi.org/10.3390/microorganisms8111762.

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Newly discovered Erwinia amylovora phages PEar1, PEar2, PEar4 and PEar6 were isolated from three different orchards in North Tunisia to study their potential as biocontrol agents. Illumina sequencing revealed that the PEar viruses carry a single-strand DNA genome between 6608 and 6801 nucleotides and belong to the Inoviridae, making them the first described filamentous phages of E. amylovora. Interestingly, phage-infected cells show a decreased swimming and swarming motility and a cocktail of the four phages can significantly reduce infection of E. amylovora in a pear bioassay, potentially making them suitable candidates for phage biocontrol.

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18

Au-Yeung, Yee Man Betty, Zheng Zeng y Jiandong Huang. "Abstract 6747: Engineering M13 filamentous phages to target dendritic cells and elicit anti-tumor immunity". Cancer Research 84, n.º 6_Supplement (22 de marzo de 2024): 6747. http://dx.doi.org/10.1158/1538-7445.am2024-6747.

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Abstract Filamentous phage is a safe and effective vaccine vector that can elicit robust immune responses by activating Toll-like receptor pathways. However, engineering neoantigen-displaying phages for cancer vaccines using phage display technology has been challenging and yielded inconsistent results. We developed a dendritic cell (DC)-targeting cancer vaccine platform with M13 filamentous phages using the phage display technology. The engineered phages express DC-targeting peptides (SLS) on p3 sites and spy-catcher proteins on p8 positions, allowing neoantigens and proteins of interest to be linked to the phage vector. We named our platform SCP (SLS-spy catcher phage). Imaging and western blot showed that spy-tagged proteins can be easily attached to SCP by simple mixing. Further studies demonstrated that targeting DCs can enhance antigen presentation and anti-cancer immunity. We tested SCP in MB49 and B16 mouse models and the serum, spleen and tumor tissues were isolated for further investigation of immune response upon treatment. We found that SCP effectively suppressed tumor growth by inducing systemic anti-tumor humoral and cell-mediated immunity. SCP also showed efficacy in late-stage tumor models. SCP treatment triggered particularly robust local anti-tumor response. Histological and flow cytometry analysis revealed increased infiltration of innate and adaptive immune cells, reduced PDL1 expression, and restricted neovascularization in the tumor microenvironment after intratumoral administration of SCP. Our study demonstrated that SCP can induce multifactorial modifications in the tumor microenvironment to impede tumor growth. SCP overcomes the limitations of traditional phage display technology, enabling a wide variety of peptides and proteins to be loaded onto the phage vectors. SCP is also cost-effective and scalable as phage production and purification processes are relatively mature. We propose that SCP can serve as a universal platform for cancer immunotherapy, and may offer novel treatment options for patients. Citation Format: Yee Man Betty Au-Yeung, Zheng Zeng, Jiandong Huang. Engineering M13 filamentous phages to target dendritic cells and elicit anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6747.

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Hille, Frank, Stefanie Gieschler, Erik Brinks y Charles M. A. P. Franz. "Characterisation of the Novel Filamentous Phage PMBT54 Infecting the Milk Spoilage Bacteria Pseudomonas carnis and Pseudomonas lactis". Viruses 15, n.º 9 (22 de agosto de 2023): 1781. http://dx.doi.org/10.3390/v15091781.

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Filamentous bacteriophages are lysogenic and pseudo-lysogenic viruses that do not lyse their host but are often continuously secreted from the infected cell. They belong to the order Tubulavirales, which encompasses three families, with the Inoviridae being the largest. While the number of identified inoviral sequences has greatly increased in recent years due to metagenomic studies, morphological and physiological characterisation is still restricted to only a few members of the filamentous phages. Here, we describe the novel filamentous phage PMBT54, which infects the spoilage-relevant Pseudomonas species P. carnis and P. lactis. Its genome is 7320 bp in size, has a mol% GC content of 48.37, and codes for 13 open-reading frames, two of which are located on the (−) strand. The virion exhibits a typical filamentous morphology and is secreted from the host cell at various lengths. The phage was shown to promote biofilm formation in both host strains and, therefore, has potential implications for milk spoilage, as biofilms are a major concern in the dairy industry.

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Ploss, Martin y Andreas Kuhn. "Kinetics of filamentous phage assembly". Physical Biology 7, n.º 4 (1 de diciembre de 2010): 045002. http://dx.doi.org/10.1088/1478-3975/7/4/045002.

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21

Nakasone, Noboru, Yasuko Honma, Claudia Toma, Tetsu Yamashiro y Masaaki Iwanaga. "Filamentous Phage fs1 ofVibrio choleraeO139". Microbiology and Immunology 42, n.º 3 (marzo de 1998): 237–39. http://dx.doi.org/10.1111/j.1348-0421.1998.tb02277.x.

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22

Renda, Brian A., Cindy Chan, Kristin N. Parent y Jeffrey E. Barrick. "Emergence of a Competence-Reducing Filamentous Phage from the Genome of Acinetobacter baylyi ADP1". Journal of Bacteriology 198, n.º 23 (19 de septiembre de 2016): 3209–19. http://dx.doi.org/10.1128/jb.00424-16.

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ABSTRACTBacterial genomes commonly contain prophage sequences as a result of past infections with lysogenic phages. Many of these integrated viral sequences are believed to be cryptic, but prophage genes are sometimes coopted by the host, and some prophages may be reactivated to form infectious particles when cells are stressed or mutate. We found that a previously uncharacterized filamentous phage emerged from the genome ofAcinetobacter baylyiADP1 during a laboratory evolution experiment. This phage has a genetic organization similar to that of theVibrio choleraeCTXϕ phage. The emergence of the ADP1 phage was associated with the evolution of reduced transformability in our experimental populations, so we named it thecompetence-reducingacinetobacter phage (CRAϕ). Knocking out ADP1 genes required for competence leads to resistance to CRAϕ infection. Although filamentous bacteriophages are known to target type IV pili, this is the first report of a phage that apparently uses a competence pilus as a receptor.A. baylyimay be especially susceptible to this route of infection because every cell is competent during normal growth, whereas competence is induced only under certain environmental conditions or in a subpopulation of cells in other bacterial species. It is possible that CRAϕ-like phages restrict horizontal gene transfer in nature by inhibiting the growth of naturally transformable strains. We also found that prophages with homology to CRAϕ exist in several strains ofAcinetobacter baumannii. These CRAϕ-likeA. baumanniiprophages encode toxins similar to CTXϕ that might contribute to the virulence of this opportunistic multidrug-resistant pathogen.IMPORTANCEWe observed the emergence of a novel filamentous phage (CRAϕ) from the genome ofAcinetobacter baylyiADP1 during a long-term laboratory evolution experiment. CRAϕ is the first bacteriophage reported to require the molecular machinery involved in the uptake of environmental DNA for infection. Reactivation and evolution of CRAϕ reduced the potential for horizontal transfer of genes via natural transformation in our experiment. Risk of infection by similar phages may limit the expression and maintenance of bacterial competence in nature. The closest studied relative of CRAϕ is theVibrio choleraeCTXϕ phage. Variants of CRAϕ are found in the genomes ofAcinetobacter baumanniistrains, and it is possible that phage-encoded toxins contribute to the virulence of this opportunistic multidrug-resistant pathogen.

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23

McCafferty, John, Andrew D. Griffiths, Greg Winter y David J. Chiswell. "Phage antibodies: filamentous phage displaying antibody variable domains". Nature 348, n.º 6301 (diciembre de 1990): 552–54. http://dx.doi.org/10.1038/348552a0.

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Stachurska, Xymena, Krzysztof Cendrowski, Kamila Pachnowska, Agnieszka Piegat, Ewa Mijowska y Paweł Nawrotek. "Nanoparticles Influence Lytic Phage T4-like Performance In Vitro". International Journal of Molecular Sciences 23, n.º 13 (28 de junio de 2022): 7179. http://dx.doi.org/10.3390/ijms23137179.

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Little is known about interactions of non-filamentous, complex-structured lytic phages and free, non-ordered nanoparticles. Emerging questions about their possible bio-sanitization co-applications or predictions of possible contact effects in the environment require testing. Therefore, we revealed the influence of various nanoparticles (NPs; SiO2, TiO2-SiO2, TiO2, Fe3O4, Fe3O4-SiO2 and SiO2-Fe3O4-TiO2) on a T4-like phage. In great detail, we investigated phage plaque-forming ability, phage lytic performance, phage progeny burst times and titers by the eclipse phase determinations. Additionally, it was proved that TEM micrographs and results of NP zeta potentials (ZP) were crucial to explain the obtained microbiological data. We propose that the mere presence of the nanoparticle charge is not sufficient for the phage to attach specifically to the NPs, consequently influencing the phage performance. The zeta potential values in the NPs are of the greatest influence. The threshold values were established at ZP < −35 (mV) for phage tail binding, and ZP > 35 (mV) for phage head binding. When NPs do not meet these requirements, phage–nanoparticle physical interaction becomes nonspecific. We also showed that NPs altered the phage lytic activity, regardless of the used NP concentration. Most of the tested nanoparticles positively influenced the phage lytic performance, except for SiO2 and Fe3O4-SiO2, with a ZP lower than −35 (mV), binding with the phage infective part—the tail.

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Saggio, I. y R. Laufer. "Biotin binders selected from a random peptide library expressed on phage". Biochemical Journal 293, n.º 3 (1 de agosto de 1993): 613–16. http://dx.doi.org/10.1042/bj2930613.

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Recombinant biotin-binding phages were affinity-selected from a random peptide library expressed on the surface of filamentous phage. Phage binding to biotinylated proteins was half-maximally inhibited by micromolar concentrations of a monobiotinylated molecule. Sequencing of the peptide inserts of selected phages led to the identification of a previously unknown biotin-binding motif, CXWXPPF(K or R)XXC. A synthetic peptide containing this sequence motif inhibited streptavidin binding to biotinylated BSA with an IC50 of 50 microM. This compound represents the shortest non-avidin biotin-binding peptide identified to date. Our results illustrate that phage display technology can be used to identify novel ligands for a small non-proteinaceous molecule.

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Addy, Hardian S., Ahmed Askora, Takeru Kawasaki, Makoto Fujie y Takashi Yamada. "The Filamentous Phage ϕRSS1 Enhances Virulence of Phytopathogenic Ralstonia solanacearum on Tomato". Phytopathology® 102, n.º 3 (marzo de 2012): 244–51. http://dx.doi.org/10.1094/phyto-10-11-0277.

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Ralstonia solanacearum is the causative agent of bacterial wilt in many important crops. ϕRSS1 is a filamentous phage that infects R. solanacearum strains. Upon infection, it alters the physiological state and the behavior of host cells. Here, we show that R. solanacearum infected by ϕRSS1 becomes more virulent on host plants. Some virulence and pathogenicity factors, such as extracellular polysaccharide (EPS) synthesis and twitching motility, increased in the bacterial host cells infected with ϕRSS1, resulting in early wilting. Tomato plants inoculated with ϕRSS1-infected bacteria wilted 2 to 3 days earlier than those inoculated with wild-type bacteria. Infection with ϕRSS1 induced early expression of phcA, the global virulence regulator. phcA expression was detected in ϕRSS1-infected cells at cell density as low as 104 CFU/ml. Filamentous phages are assembled on the host cell surface and many phage particles accumulate on the cell surface. These surface-associated phage particles (phage proteins) may change the cell surface nature (hydrophobicity) to give high local cell densities. ϕRSS1 infection also enhanced PilA and type IV pilin production, resulting in increased twitching motility.

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27

Nakamura, Michihiro, Kouhei Tsumoto, Kazunori Ishimura y Izumi Kumagai. "A Visualization Method of Filamentous Phage Infection and Phage-Derived Proteins in Escherichia coli Using Biotinylated Phages". Biochemical and Biophysical Research Communications 289, n.º 1 (noviembre de 2001): 252–56. http://dx.doi.org/10.1006/bbrc.2001.5973.

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28

Marvin, DA. "Filamentous phage structure, infection and assembly". Current Opinion in Structural Biology 8, n.º 2 (abril de 1998): 150–58. http://dx.doi.org/10.1016/s0959-440x(98)80032-8.

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29

Marciano, D. K., M. Russel y S. M. Simon. "Assembling filamentous phage occlude pIV channels". Proceedings of the National Academy of Sciences 98, n.º 16 (17 de julio de 2001): 9359–64. http://dx.doi.org/10.1073/pnas.161170398.

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30

Burritt, James B., Clifford W. Bond, Kimathi W. Doss y Algirdas J. Jesaitis. "Filamentous Phage Display of Oligopeptide Libraries". Analytical Biochemistry 238, n.º 1 (junio de 1996): 1–13. http://dx.doi.org/10.1006/abio.1996.0241.

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31

Loh, Belinda, Andreas Kuhn y Sebastian Leptihn. "The fascinating biology behind phage display: filamentous phage assembly". Molecular Microbiology 111, n.º 5 (26 de marzo de 2019): 1132–38. http://dx.doi.org/10.1111/mmi.14187.

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32

Bulssico, Julián, Irina PapukashvilI, Leon Espinosa, Sylvain Gandon y Mireille Ansaldi. "Phage-antibiotic synergy: Cell filamentation is a key driver of successful phage predation". PLOS Pathogens 19, n.º 9 (13 de septiembre de 2023): e1011602. http://dx.doi.org/10.1371/journal.ppat.1011602.

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Phages are promising tools to fight antibiotic-resistant bacteria, and as for now, phage therapy is essentially performed in combination with antibiotics. Interestingly, combined treatments including phages and a wide range of antibiotics lead to an increased bacterial killing, a phenomenon called phage-antibiotic synergy (PAS), suggesting that antibiotic-induced changes in bacterial physiology alter the dynamics of phage propagation. Using single-phage and single-cell techniques, each step of the lytic cycle of phage HK620 was studied in E. coli cultures treated with either ceftazidime, cephalexin or ciprofloxacin, three filamentation-inducing antibiotics. In the presence of sublethal doses of antibiotics, multiple stress tolerance and DNA repair pathways are triggered following activation of the SOS response. One of the most notable effects is the inhibition of bacterial division. As a result, a significant fraction of cells forms filaments that stop dividing but have higher rates of mutagenesis. Antibiotic-induced filaments become easy targets for phages due to their enlarged surface areas, as demonstrated by fluorescence microscopy and flow cytometry techniques. Adsorption, infection and lysis occur more often in filamentous cells compared to regular-sized bacteria. In addition, the reduction in bacterial numbers caused by impaired cell division may account for the faster elimination of bacteria during PAS. We developed a mathematical model to capture the interaction between sublethal doses of antibiotics and exposition to phages. This model shows that the induction of filamentation by sublethal doses of antibiotics can amplify the replication of phages and therefore yield PAS. We also use this model to study the consequences of PAS on the emergence of antibiotic resistance. A significant percentage of hyper-mutagenic filamentous bacteria are effectively killed by phages due to their increased susceptibility to infection. As a result, the addition of even a very low number of bacteriophages produced a strong reduction of the mutagenesis rate of the entire bacterial population. We confirm this prediction experimentally using reporters for bacterial DNA repair. Our work highlights the multiple benefits associated with the combination of sublethal doses of antibiotics with bacteriophages.

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Tarafder, Abul K., Andriko von Kügelgen, Adam J. Mellul, Ulrike Schulze, Dirk G. A. L. Aarts y Tanmay A. M. Bharat. "Phage liquid crystalline droplets form occlusive sheaths that encapsulate and protect infectious rod-shaped bacteria". Proceedings of the National Academy of Sciences 117, n.º 9 (18 de febrero de 2020): 4724–31. http://dx.doi.org/10.1073/pnas.1917726117.

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The opportunistic pathogenPseudomonas aeruginosais a major cause of antibiotic-tolerant infections in humans.P. aeruginosaevades antibiotics in bacterial biofilms by up-regulating expression of a symbiotic filamentous inoviral prophage, Pf4. We investigated the mechanism of phage-mediated antibiotic tolerance using biochemical reconstitution combined with structural biology and high-resolution cellular imaging. We resolved electron cryomicroscopy atomic structures of Pf4 with and without its linear single-stranded DNA genome, and studied Pf4 assembly into liquid crystalline droplets using optical microscopy and electron cryotomography. By biochemically replicating conditions necessary for antibiotic protection, we found that phage liquid crystalline droplets form phase-separated occlusive compartments around rod-shaped bacteria leading to increased bacterial survival. Encapsulation by these compartments was observed even when inanimate colloidal rods were used to mimic rod-shaped bacteria, suggesting that shape and size complementarity profoundly influences the process. Filamentous inoviruses are pervasive across prokaryotes, and in particular, several Gram-negative bacterial pathogens includingNeisseria meningitidis,Vibrio cholerae,andSalmonella entericaharbor these prophages. We propose that biophysical occlusion mediated by secreted filamentous molecules such as Pf4 may be a general strategy of bacterial survival in harsh environments.

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34

Román-Cruz, Valery C., Shannon M. Miller, Roman A. Schoener, Chase Lukasiewicz, Amelia K. Schmidt, Blair L. DeBuysscher, David Burkhart, Patrick R. Secor y Jay T. Evans. "Adjuvanted Vaccine Induces Functional Antibodies against Pseudomonas aeruginosa Filamentous Bacteriophages". Vaccines 12, n.º 2 (24 de enero de 2024): 115. http://dx.doi.org/10.3390/vaccines12020115.

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Pseudomonas aeruginosa (Pa), a WHO priority 1 pathogen, resulted in approximately 559,000 deaths globally in 2019. Pa has a multitude of host-immune evasion strategies that enhance Pa virulence. Most clinical isolates of Pa are infected by a phage called Pf that has the ability to misdirect the host-immune response and provide structural integrity to biofilms. Previous studies demonstrate that vaccination against the coat protein (CoaB) of Pf4 virions can assist in the clearance of Pa from the dorsal wound model in mice. Here, a consensus peptide was derived from CoaB and conjugated to cross-reacting material 197 (CRM197). This conjugate was adjuvanted with a novel synthetic Toll-like receptor agonist (TLR) 4 agonist, INI-2002, and used to vaccinate mice. Mice vaccinated with CoaB-CRM conjugate and INI-2002 developed high anti-CoaB peptide-specific IgG antibody titers. Direct binding of the peptide-specific antibodies to whole-phage virus particles was demonstrated by ELISA. Furthermore, a functional assay demonstrated that antibodies generated from vaccinated mice disrupted the replicative cycle of Pf phages. The use of an adjuvanted phage vaccine targeting Pa is an innovative vaccine strategy with the potential to become a new tool targeting multi-drug-resistant Pa infections in high-risk populations.

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35

Yacoby, Iftach, Marina Shamis, Hagit Bar, Doron Shabat y Itai Benhar. "Targeting Antibacterial Agents by Using Drug-Carrying Filamentous Bacteriophages". Antimicrobial Agents and Chemotherapy 50, n.º 6 (junio de 2006): 2087–97. http://dx.doi.org/10.1128/aac.00169-06.

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ABSTRACT Bacteriophages have been used for more than a century for (unconventional) therapy of bacterial infections, for half a century as tools in genetic research, for 2 decades as tools for discovery of specific target-binding proteins, and for nearly a decade as tools for vaccination or as gene delivery vehicles. Here we present a novel application of filamentous bacteriophages (phages) as targeted drug carriers for the eradication of (pathogenic) bacteria. The phages are genetically modified to display a targeting moiety on their surface and are used to deliver a large payload of a cytotoxic drug to the target bacteria. The drug is linked to the phages by means of chemical conjugation through a labile linker subject to controlled release. In the conjugated state, the drug is in fact a prodrug devoid of cytotoxic activity and is activated following its dissociation from the phage at the target site in a temporally and spatially controlled manner. Our model target was Staphylococcus aureus, and the model drug was the antibiotic chloramphenicol. We demonstrated the potential of using filamentous phages as universal drug carriers for targetable cells involved in disease. Our approach replaces the selectivity of the drug itself with target selectivity borne by the targeting moiety, which may allow the reintroduction of nonspecific drugs that have thus far been excluded from antibacterial use (because of toxicity or low selectivity). Reintroduction of such drugs into the arsenal of useful tools may help to combat emerging bacterial antibiotic resistance.

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36

Shapiro, Jason W., Elizabeth S. C. P. Williams y Paul E. Turner. "Evolution of parasitism and mutualism between filamentous phage M13 andEscherichia coli". PeerJ 4 (24 de mayo de 2016): e2060. http://dx.doi.org/10.7717/peerj.2060.

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Background.How host-symbiont interactions coevolve between mutualism and parasitism depends on the ecology of the system and on the genetic and physiological constraints of the organisms involved. Theory often predicts that greater reliance on horizontal transmission favors increased costs of infection and may result in more virulent parasites or less beneficial mutualists. We set out to understand transitions between parasitism and mutualism by evolving the filamentous bacteriophage M13 and its hostEscherichia coli.Results.The effect of phage M13 on bacterial fitness depends on the growth environment, and initial assays revealed that infected bacteria reproduce faster and to higher density than uninfected bacteria in 96-well microplates. These data suggested that M13 is, in fact, a facultative mutualist ofE. coli. We then allowedE. coliand M13 to evolve in replicated environments, which varied in the relative opportunity for horizontal and vertical transmission of phage in order to assess the evolutionary stability of this mutualism. After 20 experimental passages, infected bacteria from treatments with both vertical and horizontal transmission of phage had evolved the fastest growth rates. At the same time, phage from these treatments no longer benefited the ancestral bacteria.Conclusions.These data suggest a positive correlation between the positive effects of M13 onE. colihosts from the same culture and the negative effects of the same phage toward the ancestral bacterial genotype. The results also expose flaws in applying concepts from the virulence-transmission tradeoff hypothesis to mutualism evolution. We discuss the data in the context of more recent theory on how horizontal transmission affects mutualisms and explore how these effects influence phages encoding virulence factors in pathogenic bacteria.

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37

Addy, Hardian S., Ahmed Askora, Takeru Kawasaki, Makoto Fujie y Takashi Yamada. "Utilization of Filamentous Phage ϕRSM3 to Control Bacterial Wilt Caused by Ralstonia solanacearum". Plant Disease 96, n.º 8 (agosto de 2012): 1204–9. http://dx.doi.org/10.1094/pdis-12-11-1023-re.

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The wide host range of Ralstonia solanacearum, causal agent of bacterial wilt, and its ability to survive for long periods in the environment restrict the effectiveness of cultural and chemical control measures. The use of phages for disease control is a fast-expanding trend of plant protection with great potential to replace chemical measures. The filamentous phage ϕRSM3 that infects R. solanacearum strains and inactivates virulence on plants is a potential agent for controlling bacterial wilt in tomato. We demonstrated that inoculation of ϕRSM3-infected cells into tomato plants did not cause bacterial wilt. Instead, ϕRSM3-infected cells enhanced the expression of pathogenesis-related (PR) genes, including PR-1a, PR-2b, and PR7, in tomato plants. Moreover, pretreatment with ϕRSM-infected cells protect tomato plants from infection by virulent R. solanacearum strains. The effective dose of ϕRSM3-infected cells for disease prevention was determined to be approximately 105 CFU/ml. Because the ϕRSM3-infected cells can grow and continue to produce infectious phage particles under appropriate conditions, ϕRSM phages may serve as an efficient tool to control bacterial wilt in crops.

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38

Arza, Begoña y Jordi Félez. "The Emerging Impact of Phage Display Technology in Thrombosis and Haemostasis". Thrombosis and Haemostasis 80, n.º 09 (1998): 354–62. http://dx.doi.org/10.1055/s-0037-1615211.

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IntroducationThe phage display technology represents a powerful tool for protein and drug design because vast numbers of amino acid sequences can be rapidly explored. This review describes the origins of phage libraries, their evolution and more recent advances, including examples in the area of thrombosis and haemostasis, where the phage display approach has just begun to be used with great success.Phage display uses filamentous phages (E. coli specific phages with a filamentous shape that contain a single stranded closed circular molecule of DNA), such as M13 or fd, as vehicles for displaying foreign peptides or proteins on their surface. This is carried out by fusing the coding sequence (DNA) for the peptide or protein to the amino (N)-terminus of either full-length phage minor coat protein III (cpIII), or to phage major coat protein VIII (cpVIII), to carboxy (C)-terminal domain of cpIII or, more recently, by fusion to the C-terminus of full-length phage minor coat protein VI (cpVI) (Fig. 1). Expression of the fusion protein and its subsequent incorporation into the mature phage particle results in the foreign peptide or protein being presented on the phage surface. Thus, the linkage of each peptide or protein to its encoding genetic material [contained as part of the single-stranded viral DNA (1, 2)] represents a great advantage over conventional cloning methods.The phage display approach was first used by Smith in 1985 (3), who expressed a library of peptide sequences at the N-terminus of cpIII (3-5). This insertion allowed phage assembly and display of the peptide on the phage surface, without affecting the phage infectivity significantly. The linkage of genotype and phenotype in the phage library allowed facile isolation of clones of specific interest from pools of millions of clones by successive rounds of phage affinity selection on surfaces coated with a ligand (panning) followed by phage amplification by infecting male E. coli (Fig. 2).The foreign peptides or proteins were displayed, initially, on every copy of the coat protein, but only short peptides can be displayed in this way without altering the phage infectivity. Two systems have been developed to solve this problem. One incorporates a second native gene III or VIII in the phage genome giving a mixture of native and recombinant coat protein incorporation on the phage. The second system provides the recombinant cpIII, cpVIII or cpVI gene on a phagemid (a plasmid containing the origin of replication of filamentous phage). Phagemids can be packaged into phage particles by superinfection with a helper phage. The fusion protein is incorporated onto the surface coat, along with copies of the native coat protein encoded by the helper phage. The result is a mixture of wild-type helper phage and recombinant phagemid particles, but due to a defective origin of replication the helper phage is poorly packaged to provide minimal competition with the phagemids (6). Phages that display both native coat protein and fusion protein are infective. Therefore, the display systems can be either multivalent or monovalent. Multivalent systems make use of gene III phage constructs or gene VIII phage or phagemid constructs and give a high number of foreign domains displayed on their surface (7). Monovalent systems utilize gene III or gene VI phagemid constructs, which have a low number of foreign domains displayed on their surface, usually a single copy. Consequently, monovalent systems distinguish between low affinity and high affinity clones in panning assays (1, 8).

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39

Campos, Javier, Eriel Martínez, Karen Marrero, Yussuan Silva, Boris L. Rodríguez, Edith Suzarte, Talena Ledón y Rafael Fando. "Novel Type of Specialized Transduction forCTXφ or Its Satellite Phage RS1 Mediated by Filamentous PhageVGJφ in Vibriocholerae". Journal of Bacteriology 185, n.º 24 (15 de diciembre de 2003): 7231–40. http://dx.doi.org/10.1128/jb.185.24.7231-7240.2003.

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ABSTRACT The main virulence factor of Vibrio cholerae, the cholera toxin, is encoded by the ctxAB operon, which is contained in the genome of the lysogenic filamentous phage CTXφ. This phage transmits ctxAB genes between V. cholerae bacterial populations that express toxin-coregulated pilus (TCP), the CTXφ receptor. In investigating new forms of ctxAB transmission, we found that V. cholerae filamentous phage VGJφ, which uses the mannose-sensitive hemagglutinin (MSHA) pilus as a receptor, transmits CTXφ or its satellite phage RS1 by an efficient and highly specific TCP-independent mechanism. This is a novel type of specialized transduction consisting in the site-specific cointegration of VGJφ and CTXφ (or RS1) replicative forms to produce a single hybrid molecule, which generates a single-stranded DNA hybrid genome that is packaged into hybrid viral particles designated HybPφ (for the VGJφ/CTXφ hybrid) and HybRSφ (for the VGJφ/RS1 hybrid). The hybrid phages replicate by using the VGJφ replicating functions and use the VGJφ capsid, retaining the ability to infect via MSHA. The hybrid phages infect most tested strains more efficiently than CTXφ, even under in vitro optimal conditions for TCP expression. Infection and lysogenization with HybPφ revert the V. cholerae live attenuated vaccine strain 1333 to virulence. Our results reinforce that TCP is not indispensable for the acquisition of CTXφ. Thus, we discuss an alternative to the current accepted evolutionary model for the emergence of new toxigenic strains of V. cholerae and the importance of our findings for the development of an environmentally safer live attenuated cholera vaccine.

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40

Marciano, D. K. "An Aqueous Channel for Filamentous Phage Export". Science 284, n.º 5419 (28 de mayo de 1999): 1516–19. http://dx.doi.org/10.1126/science.284.5419.1516.

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Russel, M. y P. Model. "Thioredoxin is required for filamentous phage assembly." Proceedings of the National Academy of Sciences 82, n.º 1 (1 de enero de 1985): 29–33. http://dx.doi.org/10.1073/pnas.82.1.29.

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42

Kehoe, John W. y Brian K. Kay. "Filamentous Phage Display in the New Millennium". Chemical Reviews 105, n.º 11 (noviembre de 2005): 4056–72. http://dx.doi.org/10.1021/cr000261r.

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43

Goldbourt, Amir, Loren A. Day y Ann E. McDermott. "Intersubunit Hydrophobic Interactions in Pf1 Filamentous Phage". Journal of Biological Chemistry 285, n.º 47 (23 de agosto de 2010): 37051–59. http://dx.doi.org/10.1074/jbc.m110.119339.

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44

Stevens, Gregory B., Michael Krüger, Tatiana Latychevskaia, Peter Lindner, Andreas Plückthun y Hans-Werner Fink. "Individual filamentous phage imaged by electron holography". European Biophysics Journal 40, n.º 10 (27 de agosto de 2011): 1197–201. http://dx.doi.org/10.1007/s00249-011-0743-y.

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45

Rakonjac, Jasna y Peter Model. "Roles of pIII in filamentous phage assembly". Journal of Molecular Biology 282, n.º 1 (septiembre de 1998): 25–41. http://dx.doi.org/10.1006/jmbi.1998.2006.

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46

Russel, Marjorie. "Protein-protein Interactoins During Filamentous Phage Assembly". Journal of Molecular Biology 231, n.º 3 (junio de 1993): 689–97. http://dx.doi.org/10.1006/jmbi.1993.1320.

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47

Kaur, Tranum, Nafiseh Nafissi, Olla Wasfi, Katlyn Sheldon, Shawn Wettig y Roderick Slavcev. "Immunocompatibility of Bacteriophages as Nanomedicines". Journal of Nanotechnology 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/247427.

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Bacteriophage-based medical research provides the opportunity to develop targeted nanomedicines with heightened efficiency and safety profiles. Filamentous phages also can and have been formulated as targeted drug-delivery nanomedicines, and phage may also serve as promising alternatives/complements to antibiotics. Over the past decade the use of phage for both the prophylaxis and the treatment of bacterial infection, has gained special significance in view of a dramatic rise in the prevalence of antibiotic resistance bacterial strains. Two potential medical applications of phages are the treatment of bacterial infections and their use as immunizing agents in diagnosis and monitoring patients with immunodeficiencies. Recently, phages have been employed as gene-delivery vectors (phage nanomedicine), for nearly half a century as tools in genetic research, for about two decades as tools for the discovery of specific target-binding proteins and peptides, and for almost a decade as tools for vaccine development. As phage applications to human therapeutic development grow at an exponential rate, it will become essential to evaluate host immune responses to initial and repetitive challenges by therapeutic phage in order to develop phage therapies that offer suitable utility. This paper examines and discusses phage nanomedicine applications and the immunomodulatory effects of bacteriophage exposure and treatment modalities.

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48

Hoess, R. H., A. J. Mack, H. Walton y T. M. Reilly. "Identification of a structural epitope by using a peptide library displayed on filamentous bacteriophage." Journal of Immunology 153, n.º 2 (15 de julio de 1994): 724–29. http://dx.doi.org/10.4049/jimmunol.153.2.724.

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Abstract The screening of phage-displayed random peptide libraries has recently emerged as a powerful technique for probing Ab-Ag interactions. We have used this method to identify the epitope recognized by a mAb, CB5B10, raised against plasminogen activator inhibitor type-1 (PAI-1). Two phage libraries, displaying random hexapeptides with or without flanking cysteine residues, were screened for binding to mAb CB5B10. The selected phages were shown to contain similar peptide sequences, all of which were flanked by cysteines. When compared with the crystal structure of PAI-1, the selected peptides closely resemble the sequence of a solvent-exposed loop connecting the COOH-terminal of an alpha-helix at Phe114 to a beta-sheet at Ser119. Because of the constraints imposed by the flanking cysteine residues, the selected peptides appear to mimic the structure and the sequence of the PAI-1 epitope. Specific contacts between the amino acids displayed by the phage and the mAb were explored using site-directed mutants of the phage peptide. The effects of these substitutions on binding to the mAb correlated well with the accessibility of the corresponding residues in the PAI-1 epitope. This is the first example of the use of phage-displayed peptide libraries to identify a structural epitope.

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49

Begum, Y. A., S. Chakraborty, A. Chowdhury, A. N. Ghosh, G. B. Nair, R. B. Sack, A. M. Svennerholm y F. Qadri. "Isolation of a bacteriophage specific for CS7-expressing strains of enterotoxigenic Escherichia coli". Journal of Medical Microbiology 59, n.º 3 (1 de marzo de 2010): 266–72. http://dx.doi.org/10.1099/jmm.0.014795-0.

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Enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of childhood diarrhoea in Bangladesh. Among the virulence factors of ETEC, toxins and colonization factors (CFs) play a major role in pathogenesis. Unlike Vibrio cholerae, the relationship between ETEC and ETEC-specific phages is poorly understood and the possible role of ETEC phages in the evolution of ETEC strains in the environment is yet to be established. This study was designed specifically to isolate phages that are specific for ETEC virulence factors. Among the 49 phages isolated from 12 different surface water samples, 13 were tested against 211 ETEC strains collected from clinical and environmental sources. One phage, designated IMM-001, showed a significant specificity towards CS7 CF as it attacked all the CS7-expressing ETEC. Electron microscopic analyses showed that the isolated phage possessed an isomeric hexagonal head and a long filamentous tail. An antibody blocking method and phage neutralization assay confirmed that CS7 pilus is required for the phage infection process, indicating the role of CS7 fimbrial protein as a potential receptor for IMM-001. In summary, this study showed the presence of a lytic phage in environmental water that is specific for the CS7 CF of ETEC.

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Heilpern, Andrew J. y Matthew K. Waldor. "CTXφ Infection of Vibrio cholerae Requires the tolQRA Gene Products". Journal of Bacteriology 182, n.º 6 (15 de marzo de 2000): 1739–47. http://dx.doi.org/10.1128/jb.182.6.1739-1747.2000.

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ABSTRACT CTXφ is a lysogenic filamentous bacteriophage that encodes cholera toxin. Filamentous phages that infect Escherichia coli require both a pilus and the products of tolQRAin order to enter host cells. We have previously shown that toxin-coregulated pilus (TCP), a type IV pilus that is an essentialVibrio cholerae intestinal colonization factor, serves as a receptor for CTXφ. To test whether CTXφ also depends upontol gene products to infect V. cholerae, we identified and inactivated the V. cholerae tolQRABorthologues. The predicted amino acid sequences of V. cholerae TolQ, TolR, TolA, and TolB showed significant similarity to the corresponding E. coli sequences. V. cholerae strains with insertion mutations in tolQ,tolR, or tolA were reduced in their efficiency of CTXφ uptake by 4 orders of magnitude, whereas a strain with an insertion mutation in tolB showed no reduction in CTXφ entry. We could detect CTXφ infection of TCP− V. cholerae, albeit at very low frequencies. However, strains with mutations in both tcpA and either tolQ,tolR, or tolA were completely resistant to CTXφ infection. Thus, CTXφ, like the E. colifilamentous phages, uses both a pilus and TolQRA to enter its host. This suggests that the pathway for filamentous phage entry into cells is conserved between host bacterial species.

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