Journal articles on the topic 'Phage safety'
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Stacey, Helen J., Steven De Soir, and Joshua D. Jones. "The Safety and Efficacy of Phage Therapy: A Systematic Review of Clinical and Safety Trials." Antibiotics 11, no. 10 (September 30, 2022): 1340. http://dx.doi.org/10.3390/antibiotics11101340.
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Trials of phage therapy have not consistently reported efficacy. This contrasts with promising efficacy rates from a sizeable and compelling body of observational literature. This systematic review explores the reasons why many phage trials have not demonstrated efficacy. Four electronic databases were systematically searched for safety and/or efficacy trials of phage therapy. Sixteen trials of phage therapy were included, in which 378 patients received phage. These were divided into historical (pre-2000; N = 3; n = 76) and modern (post-2000; N = 13; n = 302) trials. All 13 modern trials concluded that phage therapy was safe. Six of the 13 modern trials were exclusively safety trials. Seven modern trials investigated both safety and efficacy; efficacy was observed in two. Two of three historical trials did not comment on safety, while adverse effects in the third likely reflected the use of phage preparations contaminated with bacterial debris. None of the historical trials contained evidence of efficacy. The evidence from trials is that phage therapy is safe. For efficacy to be observed a therapeutic amount of the right phage(s) must be delivered to the right place to treat infections containing enough susceptible bacterial cells. Trials that have not demonstrated efficacy have not fulfilled one or more elements of this principle.
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Liu, Dan, Jonas D. Van Belleghem, Christiaan R. de Vries, Elizabeth Burgener, Qingquan Chen, Robert Manasherob, Jenny R. Aronson, Derek F. Amanatullah, Pranita D. Tamma, and Gina A. Suh. "The Safety and Toxicity of Phage Therapy: A Review of Animal and Clinical Studies." Viruses 13, no. 7 (June 29, 2021): 1268. http://dx.doi.org/10.3390/v13071268.
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Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English language publications from 2008–2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimize safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found some adverse events associated with phage therapy, but serious events were extremely rare. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.
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Tang, Swee-Seong, Sudhangshu Kumar Biswas, Wen Siang Tan, Ananda Kumar Saha, and Bey-Fen Leo. "Efficacy and potential of phage therapy against multidrug resistantShigellaspp." PeerJ 7 (April 5, 2019): e6225. http://dx.doi.org/10.7717/peerj.6225.
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Shigella-infected bacillary dysentery or commonly known as Shigellosis is a leading cause of morbidity and mortality worldwide. The gradual emergence of multidrug resistantShigellaspp. has triggered the search for alternatives to conventional antibiotics. Phage therapy could be one such suitable alternative, given its proven long term safety profile as well as the rapid expansion of phage therapy research. To be successful, phage therapy will need an adequate regulatory framework, effective strategies, the proper selection of appropriate phages, early solutions to overcome phage therapy limitations, the implementation of safety protocols, and finally improved public awareness. To achieve all these criteria and successfully apply phage therapy against multidrug resistant shigellosis, a comprehensive study is required. In fact, a variety of phage-based approaches and products including single phages, phage cocktails, mutated phages, genetically engineered phages, and combinations of phages with antibiotics have already been carried out to test the applications of phage therapy against multidrug resistantShigella.This review provides a broad survey of phage treatments from past to present, focusing on the history, applications, limitations and effective solutions related to, as well as the prospects for, the use of phage therapy against multidrug resistantShigellaspp. and other multidrug resistant bacterial pathogens.
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AL-Ishaq, Raghad Khalid, Sini Skariah, and Dietrich Büsselberg. "Bacteriophage Treatment: Critical Evaluation of Its Application on World Health Organization Priority Pathogens." Viruses 13, no. 1 (December 30, 2020): 51. http://dx.doi.org/10.3390/v13010051.
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Bacteriophages represent an effective, natural, and safe strategy against bacterial infections. Multiple studies have assessed phage therapy’s efficacy and safety as an alternative approach to combat the emergence of multi drug-resistant pathogens. This systematic review critically evaluates and summarizes published articles on phages as a treatment option for Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis infection models. It also illustrates appropriate phage selection criteria, as well as recommendations for successful therapy. Published studies included in this review were identified through EMBASE, PubMed, and Web of Science databases and were published in the years between 2010 to 2020. Among 1082 identified articles, 29 studies were selected using specific inclusion and exclusion criteria and evaluated. Most studies (93.1%) showed high efficacy and safety for the tested phages, and a few studies also examined the effect of phage therapy combined with antibiotics (17.2%) and resistance development (27.6%). Further clinical studies, phage host identification, and regulatory processes are required to evaluate phage therapy’s safety and efficacy and advance their clinical use.
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Clarke, Alex, Steven De Soir, and Joshua Jones. "The Safety and Efficacy of Phage Therapy for Bone and Joint Infections: A Systematic Review." Antibiotics 9, no. 11 (November 10, 2020): 795. http://dx.doi.org/10.3390/antibiotics9110795.
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Bacterial resistance to antibiotics has catalysed interest in alternative antimicrobial strategies. Bacteriophages (phages) are viruses of bacteria with a long history of successful therapeutic use. Phage therapy is a promising antibacterial strategy for infections with a biofilm component, including recalcitrant bone and joint infections, which have significant social, financial and human impacts. Here, we report a systematic review of the safety and efficacy of phage therapy for the treatment of bone and joint infections. Three electronic databases were systematically searched for articles that reported primary data about human phage therapy for bone and joint infections. Two authors independently assessed study eligibility and performed data extraction. Seventeen reports were eligible for inclusion in this review, representing the treatment of 277 patients. A cautionary, crude, efficacy estimate revealed that 93.1% (n = 258/277) achieved clinical resolution, 3.3% (n = 9/277) had improvement and 3.6% (n = 10/277) showed no improvement. Seven of the nine reports that directly commented on the safety of phage therapy did not express safety concerns. The adverse effects reported in the remaining two were not severe and were linked to the presence of contaminating endotoxins and pre-existing liver pathology in a patient treated with high-titre intravenous phage therapy. Three other reports, from 1940–1987, offered general comments on the safety of phage therapy and documented adverse effects consistent with endotoxin co-administration concomitant with the use of raw phage lysates. Together, the reports identified by this review suggest that appropriately purified phages represent a safe and highly efficacious treatment option for complex and intractable bone and joint infections.
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Sillankorva, Sanna M., Hugo Oliveira, and Joana Azeredo. "Bacteriophages and Their Role in Food Safety." International Journal of Microbiology 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/863945.
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The interest for natural antimicrobial compounds has increased due to alterations in consumer positions towards the use of chemical preservatives in foodstuff and food processing surfaces. Bacteriophages fit in the class of natural antimicrobial and their effectiveness in controlling bacterial pathogens in agro-food industry has led to the development of different phage products already approved by USFDA and USDA. The majority of these products are to be used in farm animals or animal products such as carcasses, meats and also in agricultural and horticultural products. Treatment with specific phages in the food industry can prevent the decay of products and the spread of bacterial diseases and ultimately promote safe environments in animal and plant food production, processing, and handling. This is an overview of recent work carried out with phages as tools to promote food safety, starting with a general introduction describing the prevalence of foodborne pathogens and bacteriophages and a more detailed discussion on the use of phage therapy to prevent and treat experimentally induced infections of animals against the most common foodborne pathogens, the use of phages as biocontrol agents in foods, and also their use as biosanitizers of food contact surfaces.
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Knezevic, Petar, Aleksandra Petrovic Fabijan, Damir Gavric, Jovana Pejic, Zsolt Doffkay, and Gábor Rakhely. "Phages from Genus Bruynoghevirus and Phage Therapy: Pseudomonas Phage Delta Case." Viruses 13, no. 10 (September 30, 2021): 1965. http://dx.doi.org/10.3390/v13101965.
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The applicability and safety of bacteriophage Delta as a potential anti-Pseudomonas aeruginosa agent belonging to genus Bruynoghevirus (family Podoviridae) was characterised. Phage Delta belongs to the species Pseudomonas virus PaP3, which has been described as a temperate, with cos sites at the end of the genome. The phage Delta possesses a genome of 45,970 bp that encodes tRNA for proline (Pro), aspartic acid (Asp) and asparagine (Asn) and does not encode any known protein involved in lysogeny formation or persistence. Analysis showed that phage Delta has 182 bp direct terminal repeats at the end of genome and lysogeny was confirmed, neither upon infection at low nor at high multiplicity of infection (MOI). The turbid plaques that appear on certain host lawns can result from bacteriophage insensitive mutants that occur with higher frequency (10−4). In silico analysis showed that the genome of Delta phage does not encode any known bacterial toxin or virulence factor, determinants of antibiotic resistance and known human allergens. Based on the broad host range and high lytic activity against planktonic and biofilm cells, phage Delta represents a promising candidate for phage therapy.
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Emilia, Qori. "Challenge of bacteriophage application to improve food safety and its administration into the human gut: an article review." Journal of Microbial Systematics and Biotechnology 2, no. 1 (July 31, 2020): 10–21. http://dx.doi.org/10.37604/jmsb.v2i1.36.
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Ensuring microbial food safety has always been a challenge at every stages along the food chain. Meanwhile, healthier community lifestyle demands natural antimicrobial agents to alleviate the increasing use of chemical preservatives to address microbial contamination. Antimicrobial resistance issue has also elevated the effort to search for an alternative way to antibiotics. Bacteriophage (phage) is currently being assessed for its potency as biocontrol agent to enhance food safety and as a tool for therapeutic purpose. Prior to phage application, safety assessment must be conducted in which includes several considerations: from the discovery, toxicological aspects to the impact of phage ingestion on the gut microbiota. The gut microbiota which consist of variety of microorganisms inside the human gastrointestinal tract, cohabitate to each other. Phage is naturally present as one of microorganisms in the human gut and dynamically interacted with other microbial communities. Phage application to foods and food-contact surfaces may leave a residue and cause the phages to be ingested, which in result may alter the gut microbiota composition. Many findings have examined the relationship between gut microbiota and human health, and so is the factors affecting their modulation. This review aimed to discuss several points of view from published research papers related to the challenge of phage administration into the human gut.
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Azeredo, Joana, Jean-Paul Pirnay, Diana P. Pires, Mzia Kutateladze, Krystyna Dabrowska, Rob Lavigne, and Bob Blasdel. "Phage Therapy." WikiJournal of Medicine 8, no. 1 (2021): 4. http://dx.doi.org/10.15347/wjm/2021.004.
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Phage therapy refers to the use of bacteriophages (phages - bacterial viruses) as therapeutic agents against infectious bacterial diseases. This therapeutic approach emerged in the beginning of the 20th century but was progressively replaced by the use of antibiotics in most parts of the world after the second world war. More recently however, the alarming rise of multidrug-resistant bacteria and the consequent need for antibiotic alternatives has renewed interest in phages as antimicrobial agents. Several scientific, technological and regulatory advances have supported the credibility of a second revolution in phage therapy. Nevertheless, phage therapy still faces many challenges that include: i) the need to increase phage collections from reference phage banks; ii) the development of efficient phage screening methods for the fast identification of the therapeutic phage(s); iii) the establishment of efficient phage therapy strategies to tackle infectious biofilms; iv) the validation of feasible phage production protocols that assure quality and safety of phage preparations; and (v) the guarantee of stability of phage preparations during manufacturing, storage and transport. Moreover, current maladapted regulatory structures represent a significant hurdle for potential commercialization of phage therapeutics. This article describes the past and current status of phage therapy and presents the most recent advances in this domain.
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Bruttin, Anne, and Harald Brüssow. "Human Volunteers Receiving Escherichia coli Phage T4 Orally: a Safety Test of Phage Therapy." Antimicrobial Agents and Chemotherapy 49, no. 7 (July 2005): 2874–78. http://dx.doi.org/10.1128/aac.49.7.2874-2878.2005.
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ABSTRACT Fifteen healthy adult volunteers received in their drinking water a lower Escherichia coli phage T4 dose (103 PFU/ml), a higher phage dose (105 PFU/ml), and placebo. Fecal coliphage was detected in a dose-dependent way in volunteers orally exposed to phage. All volunteers receiving the higher phage dose showed fecal phage 1 day after exposure; this prevalence was only 50% in subjects receiving the lower phage dose. No fecal phage was detectable a week after a 2-day course of oral phage application. Oral phage application did not cause a decrease in total fecal E. coli counts. In addition, no substantial phage T4 replication on the commensal E. coli population was observed. No adverse events related to phage application were reported. Serum transaminase levels remained in the normal range, and neither T4 phage nor T4-specific antibodies were observed in the serum of the subjects at the end of the study. This is, to our knowledge, the first safety test in the recent English literature which has measured the bioavailability of oral phage in humans and is thus a first step to the rational evaluation of phage therapy for diarrheal diseases.
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Xu, Yingmin. "Phage and phage lysins: New era of bio‐preservatives and food safety agents." Journal of Food Science 86, no. 8 (July 23, 2021): 3349–73. http://dx.doi.org/10.1111/1750-3841.15843.
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Aishat, A. F., S. B. Manga, I. O. Obaroh, R. J. Bioku, and B. Abdulkadir. "An Overview on the Application of Bacteriophage Therapy in Combating Antibiotics Resistance: A Review." UMYU Journal of Microbiology Research (UJMR) 6, no. 1 (June 30, 2021): 113–19. http://dx.doi.org/10.47430/ujmr.2161.015.
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The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibioticbased, have relative advantages and disadvantages accordingly. Many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching Keywords: Antibiotic resistance; Antimicrobial; Bacteriophage; Biofilms; Multidrug resistance; Phage; Phage safety; Therapy.
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Kawacka, Iwona, Agnieszka Olejnik-Schmidt, Marcin Schmidt, and Anna Sip. "Effectiveness of Phage-Based Inhibition of Listeria monocytogenes in Food Products and Food Processing Environments." Microorganisms 8, no. 11 (November 10, 2020): 1764. http://dx.doi.org/10.3390/microorganisms8111764.
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Providing safe products and compliance of legal requirements is still a great challenge for food manufacturers regarding microbiological safety, especially in the context of Listeria monocytogenes food contamination. L. monocytogenes is a human pathogen, which, due to the ability of survival and proliferation in preservation conditions such as high salinity, acidity and refrigeration temperatures, is a significant threat to the food industry. Novel methods of elimination of the bacterial pathogen in food products and food processing environments are required. Among emerging technologies, one of the very promising solutions is using bacteriophages as natural control agents. This review focus on the major aspects of phage-based inhibition of L. monocytogenes in aspects of food safety. We describe an overview of foods and technological factors influencing the efficacy of phage use in biocontrol of L. monocytogenes. The most noteworthy are food matrix properties, phage concentration and stability, the time of phage application and product storage temperature. The combined methods, phage immobilization (active packing), pathogen resistance to phages and legislation aspects of antilisterial bacteriophage use in the food industry are also discussed.
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Wójcicki, Michał, Paulina Średnicka, Stanisław Błażejak, Iwona Gientka, Monika Kowalczyk, Paulina Emanowicz, Olga Świder, Barbara Sokołowska, and Edyta Juszczuk-Kubiak. "Characterization and Genome Study of Novel Lytic Bacteriophages against Prevailing Saprophytic Bacterial Microflora of Minimally Processed Plant-Based Food Products." International Journal of Molecular Sciences 22, no. 22 (November 18, 2021): 12460. http://dx.doi.org/10.3390/ijms222212460.
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The food industry is still searching for novel solutions to effectively ensure the microbiological safety of food, especially fresh and minimally processed food products. Nowadays, the use of bacteriophages as potential biological control agents in microbiological food safety and preservation is a promising strategy. The aim of the study was the isolation and comprehensive characterization of novel bacteriophages with lytic activity against saprophytic bacterial microflora of minimally processed plant-based food products, such as mixed leaf salads. From 43 phages isolated from municipal sewage, four phages, namely Enterobacter phage KKP 3263, Citrobacter phage KKP 3664, Enterobacter phage KKP 3262, and Serratia phage KKP 3264 have lytic activity against Enterobacter ludwigii KKP 3083, Citrobacter freundii KKP 3655, Enterobacter cloacae KKP 3082, and Serratia fonticola KKP 3084 bacterial strains, respectively. Transmission electron microscopy (TEM) and whole-genome sequencing (WGS) identified Enterobacter phage KKP 3263 as an Autographiviridae, and Citrobacter phage KKP 3664, Enterobacter phage KKP 3262, and Serratia phage KKP 3264 as members of the Myoviridae family. Genome sequencing revealed that these phages have linear double-stranded DNA (dsDNA) with sizes of 39,418 bp (KKP 3263), 61,608 bp (KKP 3664), 84,075 bp (KKP 3262), and 148,182 bp (KKP 3264). No antibiotic resistance genes, virulence factors, integrase, recombinase, or repressors, which are the main markers of lysogenic viruses, were annotated in phage genomes. Serratia phage KKP 3264 showed the greatest growth inhibition of Serratia fonticola KKP 3084 strain. The use of MOI 1.0 caused an almost 5-fold decrease in the value of the specific growth rate coefficient. The phages retained their lytic activity in a wide range of temperatures (from −20 °C to 50 °C) and active acidity values (pH from 4 to 11). All phages retained at least 70% of lytic activity at 60 °C. At 80 °C, no lytic activity against tested bacterial strains was observed. Serratia phage KKP 3264 was the most resistant to chemical factors, by maintaining high lytic activity across a broader range of pH from 3 to 11. The results indicated that these phages could be a potential biological control agent against saprophytic bacterial microflora of minimally processed plant-based food products.
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Roehnisch, Tim, Wolfgang Nagel, Thomas Boehm, Mariel Donceau, Carole Bourquin, Dilda A. Roehnisch, Beata Rutz, Christian Straka, Bertold Emmerich, and Fuat S. Oduncu. "Results of First-in-Man Phage Idiotype Vaccine Study in Patients with Multiple Myeloma." Blood 114, no. 22 (November 20, 2009): 1858. http://dx.doi.org/10.1182/blood.v114.22.1858.1858.
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Abstract Abstract 1858 Poster Board I-883 Objective: Idiotypes (Id) expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and may therefore be used as a target for vaccine immunotherapy. In this phase I/II study we have evaluated the feasibility, safety and response of phage idiotype vaccination in patients with relapsed multiple myeloma (MM) using phage displayed Id-specific proteins as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) as immunoadjuvants. Study Design: Patients received a total of 6 intradermal/subcutanous (i.d./s.c) immunizations of phage idiotype vaccines at day 1, 7, 14 and at week 4, 8 and 12. The vaccine dose started from 0.25 mg for the first 5 patients and was escalated to 1.25 mg (patient 6-10) and 2.5 mg (patient 11-15) if no dose-limiting toxicity was observed. Each vaccine contained 0.2 mg GM-CSF (Leukomax®) as adjuvant and 0.2 mg KLH (Immucothel®) as control antigen. They received all subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. Patient Characteristics: 15 patients who had previously been treated with high-dose chemotherapy (HDT) followed by peripheral blood progenitor cell (PBPC) transplantation entered this study. All patients were in a beginning relapse after high dose therapy at the time of vaccination. Patients with fulminant relapse or patients with active infection and hematopoetic insufficiency after HDT were excluded. Results: The results of this first-in-man phase I/II trial for phage-based idiotype vaccination clearly demonstrated the feasibility, safety and excellent tolerability of the phage vaccination whereas local skin reactions were the most frequent side effects. Furthermore, we were able to gather precious data regarding the immunology of phage vaccines in man. We could confirm our preclinical data, that phages are good immunogens, capable of inducing a strong immune response mainly of IgG1-type and therefore enabling ADCC and CDC immune response. Altogether these data suggest, that phage idiotype vaccines has the potential to exert a beneficial effect especially in patients with minimal residual disease. Strikingly, the immune response of phages compared to the well-known KLH particles showed > 10 time higher antibody titer than KLH, which emphasize the prominent immunogenicity of the phages. Overall these data pinpoint to a promising role of phage vaccination for the immunotherapy of cancer but further studies are necessary to evaluate the full potential of phage vaccines. Disclosures: Roehnisch: Apalexo Biotechnologie GmbH: Research Funding. Nagel:Apalexo Biotechnologie GmbH: Research Funding. Donceau:Apalexo Biotechnologie GmbH: Research Funding. Bourquin:Apalexo Biotechnologie GmbH: Research Funding.
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Kim, Hyun Young, Rachel Yoon Kyung Chang, Sandra Morales, and Hak-Kim Chan. "Bacteriophage-Delivering Hydrogels: Current Progress in Combating Antibiotic Resistant Bacterial Infection." Antibiotics 10, no. 2 (January 29, 2021): 130. http://dx.doi.org/10.3390/antibiotics10020130.
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Antibiotic resistance remains as an unresolved global challenge in the health care system, posing serious threats to global health. As an alternative to antibiotics, bacteriophage (phage) therapy is rising as a key to combating antibiotic-resistant bacterial infections. In order to deliver a phage to the site of infection, hydrogels have been formulated to incorporate phages, owing to its favorable characteristics in delivering biological molecules. This paper reviews the formulation of phage-delivering hydrogels for orthopedic implant-associated bone infection, catheter-associated urinary tract infection and trauma-associated wound infection, with a focus on the preparation methods, stability, efficacy and safety of hydrogels as phage carriers.
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Kolenda, Camille, Mathieu Medina, Mélanie Bonhomme, Floriane Laumay, Tiphaine Roussel-Gaillard, Patricia Martins-Simoes, Anne Tristan, Fabrice Pirot, Tristan Ferry, and Frédéric Laurent. "Phage Therapy against Staphylococcus aureus: Selection and Optimization of Production Protocols of Novel Broad-Spectrum Silviavirus Phages." Pharmaceutics 14, no. 9 (September 6, 2022): 1885. http://dx.doi.org/10.3390/pharmaceutics14091885.
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Background: Phage therapy a promising antimicrobial strategy to address antimicrobial resistance for infections caused by the major human pathogen Staphylococcus aureus. Development of therapeutic phages for human use should follow pharmaceutical standards, including selection of strictly lytic bacteriophages with high therapeutic potential and optimization of their production process. Results: Here, we describe three novel Silviavirus phages active against 82% of a large collection of strains (n = 150) representative of various methicillin-susceptible and -resistant S. aureus clones circulating worldwide. We also investigated the optimization of the efficiency and safety of phage amplification protocols. To do so, we selected a well-characterized bacterial strain in order to (i) maximize phage production yields, reaching phage titres of 1011 PFU/mL in only 4 h; and (ii) facilitate phage purity while minimizing the risk of the presence of contaminants originating from the bacterial host; i.e., secreted virulence factors or induced temperate phages. Conclusions: In sum, we propose a quality-by-design approach for the amplification of broad-spectrum anti-S. aureus phages, facilitating the subsequent steps of the manufacturing process; namely, purification and quality control.
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Gill, J. J. "118 Phage applications in animal agriculture and food safety." Journal of Animal Science 94, suppl_1 (February 1, 2016): 57–58. http://dx.doi.org/10.2527/ssasas2015-118.
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Pirnay, Jean-Paul, Bob G. Blasdel, Laurent Bretaudeau, Angus Buckling, Nina Chanishvili, Jason R. Clark, Sofia Corte-Real, et al. "Quality and Safety Requirements for Sustainable Phage Therapy Products." Pharmaceutical Research 32, no. 7 (January 14, 2015): 2173–79. http://dx.doi.org/10.1007/s11095-014-1617-7.
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Khatami, Ameneh, David A. Foley, Morgyn S. Warner, Elizabeth H. Barnes, Anton Y. Peleg, Jian Li, Stephen Stick, et al. "Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial." BMJ Open 12, no. 12 (December 2022): e065401. http://dx.doi.org/10.1136/bmjopen-2022-065401.
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IntroductionThere has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy.Methods and analysisWe propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia’s Therapeutic Goods Administration Special Access Scheme. A phage product with highin vitroactivity against the targeted pathogen(s) must be available in line with relevant regulatory requirements. We aim to recruit 50–100 patients over 5 years, from any public or private hospitals in Australia. The standardised protocol will specify clinical assessments and biological sampling at scheduled time points. The primary outcome is safety at day 29, assessed by the frequency of adverse events, and overseen by an independent Data Safety Monitoring Board. Secondary outcomes include long-term safety (frequency of adverse events until at least 6 months following phage therapy), and feasibility, measured as the proportion of participants with>80% of minimum data available for analysis. Additional endpoints assessed include clinical response, patient/guardian reported quality of life measures, phage pharmacokinetics, human host immune responses and microbiome analysis. All trial outcomes will be summarised and presented using standard descriptive statistics.Ethics and disseminationParticipant inclusion will be dependent on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Sydney Children’s Hospitals Network Human Research Ethics Committee in December 2021 (Reference 2021/ETH11861). In addition to publication in a peer-reviewed scientific journal, a lay summary of study outcomes will be made available for participants and the public on the Phage Australia website (https://www.phageaustralia.org/).Trial registration numberRegistered on ANZCTR, 10 November 2021 (ACTRN12621001526864; WHO Universal Trial Number: U1111-1269-6000).
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Jun, Soo Youn, Gi Mo Jung, Seong Jun Yoon, Yun-Jaie Choi, Woo Suk Koh, Kyoung Sik Moon, and Sang Hyeon Kang. "Preclinical Safety Evaluation of Intravenously Administered SAL200 Containing the Recombinant Phage Endolysin SAL-1 as a Pharmaceutical Ingredient." Antimicrobial Agents and Chemotherapy 58, no. 4 (January 21, 2014): 2084–88. http://dx.doi.org/10.1128/aac.02232-13.
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ABSTRACTPhage endolysins have received increasing attention as potent antibacterial agents. However, although safety evaluation is a prerequisite for the drug development process, a good laboratory practice (GLP)-compliant safety evaluation has not been reported for phage endolysins. A safety evaluation of intravenously administered SAL200 (containing phage endolysin SAL-1) was conducted according to GLP standards. No animals died in any of the safety evaluation studies. In general toxicity studies, intravenously administered SAL200 showed no sign of toxicity in rodent single- and repeated-dose toxicity studies. In the dog repeated-dose toxicity test, there were no abnormal findings, with the exception of transient abnormal clinical signs that were observed in some dogs when daily injection of SAL200 was continued for more than 1 week. In safety pharmacology studies, there were also no signs of toxicity in the central nervous and respiratory system function tests. In the cardiovascular function test, there were no abnormal findings in all tested dogs after the first and second administrations, but transient abnormalities were observed after the third and fourth administrations (2 or 3 weeks after the initial administration). All abnormal findings observed in these safety evaluation studies were slight to mild, were apparent only transiently after injection, and resolved quickly. The safety evaluation results for SAL200 support the implementation of an exploratory phase I clinical trial and underscore the potential of SAL200 as a new drug. We have designed an appropriate phase I clinical trial based on the results of this study.
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Kaur, Tranum, Nafiseh Nafissi, Olla Wasfi, Katlyn Sheldon, Shawn Wettig, and 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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Abdelrahman, Fatma, Maheswaran Easwaran, Oluwasegun I. Daramola, Samar Ragab, Stephanie Lynch, Tolulope J. Oduselu, Fazal Mehmood Khan, et al. "Phage-Encoded Endolysins." Antibiotics 10, no. 2 (January 28, 2021): 124. http://dx.doi.org/10.3390/antibiotics10020124.
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Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.
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McCallin, Shawna, and Harald Brüssow. "Phage therapy: an alternative or adjunct to antibiotics?" Emerging Topics in Life Sciences 1, no. 1 (April 21, 2017): 105–16. http://dx.doi.org/10.1042/etls20170005.
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Phage therapy is currently discussed as an alternative or adjunct to antibiotics whose activity is increasingly compromised by the emergence of antibiotic-resistant bacterial pathogens. The idea to use lytic bacterial viruses as antimicrobial agents is nearly a century old and is common practice in Eastern Europe. However, safety concerns and lack of controlled clinical trials proving the efficacy of phage therapy have hampered its wider medical use in the West. The present review analyzes safety aspects and compares successful with unsuccessful phage therapy clinical trials to identify potential factors determining success and failure of this approach.
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El Haddad, Lynn, Cynthia P. Harb, Mark Stibich, Roy F. Chemaly, and Roy F. Chemaly. "735. Bacteriophage Therapy Improves Survival of Galleria mellonella Larvae Injected with Vancomycin-Resistant Enterococcus faecium." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S329. http://dx.doi.org/10.1093/ofid/ofz360.803.
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Abstract Background Vancomycin-resistant Enterococcus faecium (VRE) is a major multidrug-resistant organism which may cause infection or colonization in hematopoietic cell transplant (HCT) patients. The use of VRE-specific bacteriophages (phages) may potentially help eradicate VRE colonization and subsequent infections. To test the efficacy and safety of phages against VRE in vivo, a cocktail combining four phages was used in a VRE-infected larva model. Methods The pre-screening model Greater Wax Galleria mellonella larva was used in this study. Larvae were infected with VRE by injecting a VRE strain isolated from stools of a VRE-colonized HCT patient at a concentration of 107 colony-forming units/10 μL. A single phage (MDA1) or a phage cocktail (MDA1, MDA2, MDA3, and MDA4) were also injected at a concentration of 106 colony-forming units/10 μL. Two model groups were tested; a prevention group (PG) and a treatment group (TG). For the PG, phages were administered 1 hour before bacterial injection whereas the TG were injected with phages 1 hour post bacterial injection. Control groups included larvae injected with bacteria alone, phages alone (to measure toxicity due to phage administration), sterile media (to measure any lethal effects due to physical trauma from the injection), or without any manipulation. Every group was composed of 5 larvae. The insect’s health state was observed and scored after 8 hours of incubation at 37ºC using a published health index scoring system. Results Phages improved survival of VRE-infected larvae (table). Only 32% of the VRE-infected larvae survived after 8 hours of infection whereas more than 80% survived when adding phages, whether phages were administered before or after VRE infection. The phage cocktail was shown to be more effective than the single phage MDA1 in improving survival (66% vs. 82% survival). Injecting larvae with phages alone was safe as the same survival rate was observed when compared with those injected with sterile media or those without manipulation. Conclusion The use of larva model G. mellonella allows for rapid and efficient screening of the bacterial virulence and phage efficacy and safety. Such results highlight the feasibility and the potential impact of phage therapy on VRE colonization and infections. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix: Advisory Board, Research Grant; Clinigen: Advisory Board; Merck: Advisory Board, Consultant, Grant/Research Support, Research Grant, Speaker’s Bureau; Oxford immunotec: Consultant, Grant/Research Support; Shire: Research Grant, Speaker’s Bureau; Viracor: Grant/Research Support.
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Yan, Ting, Lu Liang, Ping Yin, Yang Zhou, Ashraf Mahdy Sharoba, Qun Lu, Xingxing Dong, Kun Liu, Ian F. Connerton, and Jinquan Li. "Application of a Novel Phage LPSEYT for Biological Control of Salmonella in Foods." Microorganisms 8, no. 3 (March 12, 2020): 400. http://dx.doi.org/10.3390/microorganisms8030400.
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Salmonella is a leading cause of foodborne diseases, and in recent years, many isolates have exhibited a high level of antibiotic resistance, which has led to huge pressures on public health. Phages are a promising strategy to control food-borne pathogens. In this study, one of our environmental phage isolates, LPSEYT, was to be able to restrict the growth of zoonotic Salmonella enterica in vitro over a range of multiplicity of infections. Phage LPSEYT exhibited wide-ranging pH and thermal stability and rapid reproductive activity with a short latent period and a large burst size. Phage LPSEYT demonstrated potential efficiency as a biological control agent against Salmonella in a variety of food matrices, including milk and lettuce. Morphological observation, comparative genomic, and phylogenetic analysis revealed that LPSEYT does not belong to any of the currently identified genera within the Myoviridae family, and we suggest that LPSEYT represents a new genus, the LPSEYTvirus. This study contributes a phage database, develops beneficial phage resources, and sheds light on the potential application value of phages LPSEYT on food safety.
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Jończyk-Matysiak, Ewa, Barbara Owczarek, Ewa Popiela, Kinga Świtała-Jeleń, Paweł Migdał, Martyna Cieślik, Norbert Łodej, et al. "Isolation and Characterization of Phages Active against Paenibacillus larvae Causing American Foulbrood in Honeybees in Poland." Viruses 13, no. 7 (June 23, 2021): 1217. http://dx.doi.org/10.3390/v13071217.
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The aim of this study was the isolation and characterization, including the phage effect on honeybees in laboratory conditions, of phages active against Paenibacillus larvae, the causative agent of American Foulbrood—a highly infective and easily spreading disease occurring in honeybee larva, and subsequently the development of a preparation to prevent and treat this dangerous disease. From the tested material (over 2500 samples) 35 Paenibacillus spp. strains were obtained and used to search for phages. Five phages specific to Paenibacillus were isolated and characterized (ultrastructure, morphology, biological properties, storage stability, and genome sequence). The characteristics were performed to obtain knowledge of their lytic potential and compose the final phage cocktail with high antibacterial potential and intended use of future field application. Preliminary safety studies have also been carried out on healthy bees, which suggest that the phage preparation administered is harmless.
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Łusiak-Szelachowska, Marzanna, Beata Weber-Dąbrowska, Maciej Żaczek, Jan Borysowski, and Andrzej Górski. "The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?" Microorganisms 8, no. 12 (December 16, 2020): 2012. http://dx.doi.org/10.3390/microorganisms8122012.
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The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested. Furthermore, most phages found at different sites in the human body are temperate, so their therapeutic effects and their potential beneficial effects remain unclear. Hence, far, no correlation has been observed between the presence of widespread crAssphage in the human population and human health and diseases. Here, we emphasize the beneficial effects of phage transfer in fecal microbiota transplantation (FMT) in Clostridioides difficile infection. The safety of phage use in gastrointestinal disorders has been demonstrated in clinical studies. The significance of phages in the FMT as well as in gastrointestinal disorders remains to be established. An explanation of the multifaceted role of endogenous phages for the development of phage therapy is required.
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Abril, Ana G., Mónica Carrera, Vicente Notario, Ángeles Sánchez-Pérez, and Tomás G. Villa. "The Use of Bacteriophages in Biotechnology and Recent Insights into Proteomics." Antibiotics 11, no. 5 (May 13, 2022): 653. http://dx.doi.org/10.3390/antibiotics11050653.
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Phages have certain features, such as their ability to form protein–protein interactions, that make them good candidates for use in a variety of beneficial applications, such as in human or animal health, industry, food science, food safety, and agriculture. It is essential to identify and characterize the proteins produced by particular phages in order to use these viruses in a variety of functional processes, such as bacterial detection, as vehicles for drug delivery, in vaccine development, and to combat multidrug resistant bacterial infections. Furthermore, phages can also play a major role in the design of a variety of cheap and stable sensors as well as in diagnostic assays that can either specifically identify specific compounds or detect bacteria. This article reviews recently developed phage-based techniques, such as the use of recombinant tempered phages, phage display and phage amplification-based detection. It also encompasses the application of phages as capture elements, biosensors and bioreceptors, with a special emphasis on novel bacteriophage-based mass spectrometry (MS) applications.
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Nale, Janet Y., and Martha RJ Clokie. "Preclinical data and safety assessment of phage therapy in humans." Current Opinion in Biotechnology 68 (April 2021): 310–17. http://dx.doi.org/10.1016/j.copbio.2021.03.002.
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Speck, Peter, and Anthony Smithyman. "Safety and efficacy of phage therapy via the intravenous route." FEMS Microbiology Letters 363, no. 3 (December 20, 2015): fnv242. http://dx.doi.org/10.1093/femsle/fnv242.
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Roach, Dwayne R., and Laurent Debarbieux. "Phage therapy: awakening a sleeping giant." Emerging Topics in Life Sciences 1, no. 1 (April 21, 2017): 93–103. http://dx.doi.org/10.1042/etls20170002.
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For a century, bacterial viruses called bacteriophages have been exploited as natural antibacterial agents. However, their medicinal potential has not yet been exploited due to readily available and effective antibiotics. After years of extensive use, both properly and improperly, antibiotic-resistant bacteria are becoming more prominent and represent a worldwide public health threat. Most importantly, new antibiotics are not progressing at the same rate as the emergence of resistance. The therapeutic modality of bacteriophages, called phage therapy, offers a clinical option to combat bacteria associated with diseases. Here, we discuss traditional phage therapy approaches, as well as how synthetic biology has allowed for the creation of designer phages for new clinical applications. To implement these technologies, several key aspects and challenges still need to be addressed, such as narrow spectrum, safety, and bacterial resistance. We will summarize our current understanding of how phage treatment elicits mammalian host immune responses, as well bacterial phage resistance development, and the potential impact each will have on phage therapy effectiveness. We conclude by discussing the need for a paradigm shift on how phage therapy strategies are developed.
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Wienhold, Sandra-Maria, Jasmin Lienau, and Martin Witzenrath. "Towards Inhaled Phage Therapy in Western Europe." Viruses 11, no. 3 (March 23, 2019): 295. http://dx.doi.org/10.3390/v11030295.
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The emergence of multidrug-resistant bacteria constitutes a great challenge for modern medicine, recognized by leading medical experts and politicians worldwide. Rediscovery and implementation of bacteriophage therapy by Western medicine might be one solution to the problem of increasing antibiotic failure. In some Eastern European countries phage therapy is used for treating infectious diseases. However, while the European Medicines Agency (EMA) advised that the development of bacteriophage-based therapies should be expedited due to its significant potential, EMA emphasized that phages cannot be recommended for approval before efficacy and safety have been proven by appropriately designed preclinical and clinical trials. More evidence-based data is required, particularly in the areas of pharmacokinetics, repeat applications, immunological reactions to the application of phages as well as the interactions and effects on bacterial biofilms and organ-specific environments. In this brief review we summarize advantages and disadvantages of phage therapy and discuss challenges to the establishment of phage therapy as approved treatment for multidrug-resistant bacteria.
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Hyla, Kinga, Izabela Dusza, and Aneta Skaradzińska. "Recent Advances in the Application of Bacteriophages against Common Foodborne Pathogens." Antibiotics 11, no. 11 (November 2, 2022): 1536. http://dx.doi.org/10.3390/antibiotics11111536.
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Bacteriophage potential in combating bacterial pathogens has been recognized nearly since the moment of discovery of these viruses at the beginning of the 20th century. Interest in phage application, which initially focused on medical treatments, rapidly spread throughout different biotechnological and industrial fields. This includes the food safety sector in which the presence of pathogens poses an explicit threat to consumers. This is also the field in which commercialization of phage-based products shows the greatest progress. Application of bacteriophages has gained special attention particularly in recent years, presumably due to the potential of conventional antibacterial strategies being exhausted. In this review, we present recent findings regarding phage application in fighting major foodborne pathogens, including Salmonella spp., Escherichia coli, Yersinia spp., Campylobacter jejuni and Listeria monocytogenes. We also discuss advantages of bacteriophage use and challenges facing phage-based antibacterial strategies, particularly in the context of their widespread application in food safety.
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Santos, S. B., E. Fernandes, C. M. Carvalho, S. Sillankorva, V. N. Krylov, E. A. Pleteneva, O. V. Shaburova, A. Nicolau, E. C. Ferreira, and J. Azeredo. "Selection and Characterization of a Multivalent Salmonella Phage and Its Production in a Nonpathogenic Escherichia coli Strain." Applied and Environmental Microbiology 76, no. 21 (September 3, 2010): 7338–42. http://dx.doi.org/10.1128/aem.00922-10.
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ABSTRACT We report the selection and amplification of the broad-host-range Salmonella phage phi PVP-SE1 in an alternative nonpathogenic host. The lytic spectrum and the phage DNA restriction profile were not modified upon replication in Escherichia coli Bl21, suggesting the possibility of producing this phage in a nonpathogenic host, contributing to the safety and easier approval of a product based on this Salmonella biocontrol agent.
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Steele, Angharad, Helen J. Stacey, Steven de Soir, and Joshua D. Jones. "The Safety and Efficacy of Phage Therapy for Superficial Bacterial Infections: A Systematic Review." Antibiotics 9, no. 11 (October 29, 2020): 754. http://dx.doi.org/10.3390/antibiotics9110754.
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Superficial bacterial infections, such as dermatological, burn wound and chronic wound/ulcer infections, place great human and financial burdens on health systems globally and are often complicated by antibiotic resistance. Bacteriophage (phage) therapy is a promising alternative antimicrobial strategy with a 100-year history of successful application. Here, we report a systematic review of the safety and efficacy of phage therapy for the treatment of superficial bacterial infections. Three electronic databases were systematically searched for articles that reported primary data about human phage therapy for dermatological, burn wound or chronic wound/ulcer infections secondary to commonly causative bacteria. Two authors independently assessed study eligibility and performed data extraction. Of the 27 eligible reports, eight contained data on burn wound infection (n = 156), 12 on chronic wound/ulcer infection (n = 327) and 10 on dermatological infections (n = 1096). Cautionary pooled efficacy estimates from the studies that clearly reported efficacy data showed clinical resolution or improvement in 77.5% (n = 111) of burn wound infections, 86.1% (n = 310) of chronic wound/ulcer infections and 94.14% (n = 734) of dermatological infections. Over half of the reports that commented on safety (n = 8/15), all published in or after 2002, did not express safety concerns. Seven early reports (1929–1987), described adverse effects consistent with the administration of raw phage lysate and co-administered bacterial debris or broth. This review strongly suggests that the use of purified phage to treat superficial bacterial infections can be highly effective and, by various routes of administration, is safe and without adverse effects.
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Onsea, Jolien, Saartje Uyttebroek, Baixing Chen, Jeroen Wagemans, Cédric Lood, Laura Van Gerven, Isabel Spriet, et al. "Bacteriophage Therapy for Difficult-to-Treat Infections: The Implementation of a Multidisciplinary Phage Task Force (The PHAGEFORCE Study Protocol)." Viruses 13, no. 8 (August 5, 2021): 1543. http://dx.doi.org/10.3390/v13081543.
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In times where only a few novel antibiotics are to be expected, antimicrobial resistance remains an expanding global health threat. In case of chronic infections caused by therapy-resistant pathogens, physicians have limited therapeutic options, which are often associated with detrimental consequences for the patient. This has resulted in a renewed interest in alternative strategies, such as bacteriophage (phage) therapy. However, there are still important hurdles that currently impede the more widespread implementation of phage therapy in clinical practice. First, the limited number of good-quality case series and clinical trials have failed to show the optimal application protocol in terms of route of administration, frequency of administration, treatment duration and phage titer. Second, there is limited information on the systemic effects of phage therapy. Finally, in the past, phage therapy has been applied intuitively in terms of the selection of phages and their combination as parts of phage cocktails. This has led to an enormous heterogeneity in previously published studies, resulting in a lack of reliable safety and efficacy data for phage therapy. We hereby present a study protocol that addresses these scientific hurdles using a multidisciplinary approach, bringing together the experience of clinical, pharmaceutical and molecular microbiology experts.
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Zhong, Zeyan, Jean-Guillaume Emond-Rheault, Sudhakar Bhandare, Roger Lévesque, and Lawrence Goodridge. "Bacteriophage-Induced Lipopolysaccharide Mutations in Escherichia coli Lead to Hypersensitivity to Food Grade Surfactant Sodium Dodecyl Sulfate." Antibiotics 9, no. 9 (August 28, 2020): 552. http://dx.doi.org/10.3390/antibiotics9090552.
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Bacteriophages (phages) are considered as one of the most promising antibiotic alternatives in combatting bacterial infectious diseases. However, one concern of employing phage application is the emergence of bacteriophage-insensitive mutants (BIMs). Here, we isolated six BIMs from E. coli B in the presence of phage T4 and characterized them using genomic and phenotypic methods. Of all six BIMs, a six-amino acid deletion in glucosyltransferase WaaG likely conferred phage resistance by deactivating the addition of T4 receptor glucose to the lipopolysaccharide (LPS). This finding was further supported by the impaired phage adsorption to BIMs and glycosyl composition analysis which quantitatively confirmed the absence of glucose in the LPS of BIMs. Since LPSs actively maintain outer membrane (OM) permeability, phage-induced truncations of LPSs destabilized the OM and sensitized BIMs to various substrates, especially to the food-grade surfactant sodium dodecyl sulfate (SDS). This hypersensitivity to SDS was exploited to design a T4–SDS combination which successfully prevented the generation of BIMs and eliminated the inoculated bacteria. Collectively, phage-driven modifications of LPSs immunized BIMs from T4 predation but increased their susceptibilities as a fitness cost. The findings of this study suggest a novel strategy to enhance the effectiveness of phage-based food safety interventions.
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Hemalata, V. B., Ajay Kumar Oli, and D. B. M. Virupakshaiah. "Evaluating of Phage as Bio-control Agent in Enumeration of Food Borne Pathogenic Pseudomonas aeruginosa." Journal of Pure and Applied Microbiology 14, no. 3 (September 29, 2020): 2115–28. http://dx.doi.org/10.22207/jpam.14.3.52.
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Phage acts as a bio-controlling agent to overcome chemical supplement in the treatment food pathogens. Bacterial pathogens mainly cause food borne diseases; these are harmful to human health and also threat to nutritional economy. Due to aggregating in the multidrug resistance among the pathogens, the conventional methods for food safety are drawn in the use of chemicals and causes toxicity. In our present study, the P. aeruginosa isolates were determined from food samples on specific Cetrimide agar and a specific phage was isolated against the strain. The microbial enumeration growth was carried out on meat samples. The preservative activity was performed on banana samples. The present phage has indicated a prominent agent in enumeration of microbial growth against meat and mutton samples. It also showed a quality preservative for storage in banana samples. The potential advantage of using phage is their specificity and ability to multiply; hence, it can be used in food safety and provide a natural alternative to conventional synthetic preservatives used in food industries. The phage has ability in decreasing the growth microbes in food samples and long storage as preservative in fruits.
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Pelyuntha, Wattana, Ananya Yafa, Ruttayaporn Ngasaman, Mingkwan Yingkajorn, Kridda Chukiatsiri, Nidanut Champoochana, and Kitiya Vongkamjan. "Oral Administration of a Phage Cocktail to Reduce Salmonella Colonization in Broiler Gastrointestinal Tract—A Pilot Study." Animals 12, no. 22 (November 9, 2022): 3087. http://dx.doi.org/10.3390/ani12223087.
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Salmonella contamination in poultry meat products can lead to serious foodborne illness and economic loss from product recalls. It is crucial to control Salmonella contamination in poultry from farm to fork. Bacteriophages (phages) are viruses of bacteria that offer several advantages, especially their specificity to target bacteria. In our study, three Salmonella phages (vB_SenS_KP001, vB_SenS_KP005, and vB_SenS_WP110) recovered from a broiler farm and wastewater treatment stations showed high lysis ability ranging from 85.7 to 96.4% on over 56 serovars of Salmonella derived from several sources, including livestock and a broiler farm environment. A three-phage cocktail reduced S. Enteritidis and S. Typhimurium, in vitro by 3.9 ± 0.0 and 3.9 ± 0.2 log units at a multiplicity of infection (MOI) of 103 and 3.8 ± 0.4 and 4.1 ± 0.2 log units at MOI of 104 after 6 h post-phage treatment. A developed phage cocktail did not cause phage resistance in Salmonella during phage treatments for three passages. Phages could survive under simulated chicken gastrointestinal conditions in the presence of gastric acid for 2 h (100.0 ± 0.0 % survivability), bile salt for 1 h (98.1 ± 1.0 % survivability), and intestinal fluid for 4 h (100 ± 0.0 % survivability). Each phage was in the phage cocktail at a concentration of up to 9.0 log PFU/mL. These did not cause any cytotoxicity to human fibroblast cells or Caco-2 cells as indicated by the percent of cell viability, which remained nearly 100% as compared with the control during 72 h of co-culture. The phage cocktail was given to broilers raised in commercial conditions at a 9 log PFU/dose for five doses, while naturally occurring Salmonella cells colonized in the gastrointestinal tract of broilers were significantly reduced as suggested by a considerably lower Salmonella prevalence from over 70 to 0% prevalence after four days of phage treatment. Our findings suggest that a phage cocktail is an effective biocontrol agent to reduce Salmonella present in the guts of broilers, which can be applied to improve food safety in broiler production.
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Cof fey, Brid, Susan Mills, Aidan Coffey, Olivia McAuliffe, and R. Paul Ross. "Phage and Their Lysins as Biocontrol Agents for Food Safety Applications." Annual Review of Food Science and Technology 1, no. 1 (April 2010): 449–68. http://dx.doi.org/10.1146/annurev.food.102308.124046.
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El-Shibiny, A., S. El-Sahhar, and M. Adel. "Phage applications for improving food safety and infection control in Egypt." Journal of Applied Microbiology 123, no. 2 (July 12, 2017): 556–67. http://dx.doi.org/10.1111/jam.13500.
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Würstle, Silvia, Jana Stender, Jens André Hammerl, Kilian Vogele, Kathrin Rothe, Christian Willy, and Joachim Jakob Bugert. "Practical Assessment of an Interdisciplinary Bacteriophage Delivery Pipeline for Personalized Therapy of Gram-Negative Bacterial Infections." Pharmaceuticals 15, no. 2 (February 2, 2022): 186. http://dx.doi.org/10.3390/ph15020186.
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Despite numerous advances in personalized phage therapy, smooth logistics are challenging, particularly for multidrug-resistant Gram-negative bacterial infections requiring high numbers of specific lytic phages. We conducted this study to pave the way for efficient logistics for critically ill patients by (1) closely examining and improving a current pipeline under realistic conditions, (2) offering guidelines for each step, leading to safe and high-quality phage supplies, and (3) providing a tool to evaluate the pipeline’s efficiency. Due to varying stipulations for quality and safety in different countries, we focused the pipeline on all steps up to a required phage product by a cell-free extract system. The first of three study runs included patients with respiratory bacterial infections from four intensive care units, and it revealed a cumulative time of up to 23 days. Ultimately, adjustment of specific set points of the vulnerable components of the pipeline, phage isolation, and titration increased the pipeline’s efficiency by 15% and decreased the maximum required time to 13 days. We present a site-independent practical approach to establish and optimize pipelines for personalized phage delivery, the co-organization of pipeline components between different institutions, non-binding guidelines for every step, and an efficiency check for phage laboratories.
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Coetzer, Theresa L., and Sonja B. Lauterbach. "Safety of Total Therapy III for Newly Diagnosed Multiple Myeloma: Preliminary Analysis of 62 Consecutive Patients. Safety of Total Therapy III for Newly Diagnosed Multiple Myeloma: Preliminary Analysis of 62 Consecutive Patients." Blood 104, no. 11 (November 16, 2004): 1582. http://dx.doi.org/10.1182/blood.v104.11.1582.1582.
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Abstract Malaria is one of the world’s major health problems, causing millions of deaths every year, primarily in Africa. The disease is caused by Plasmodium parasites, which invade and destroy human erythrocytes. Of the four species infecting humans, Plasmodium falciparum is responsible for the greatest morbidity and mortality burden. The erythrocyte membrane plays a vital role in all aspects of the pathogenic phase of the parasite’s life cycle and the protein-protein interactions between host and parasite are a key focus of research. Spectrin is the main structural protein in the erythrocyte membrane skeleton and phage-display technology was used to probe the interaction between P falciparum peptide fragments and human erythrocyte spectrin. A phage-display library was constructed by isolating mRNA from P falciparum strain FCR-3, which was reverse transcribed using two-base anchored oligodT primers. Linkers facilitating directional cloning were added to the cDNA, followed by insertion into a gene encoding the 10B capsid protein of the T7 bacteriophage vector. The vector was packaged into viral particles and the library amplified using Escherichia coli as a host. The presence and size of inserts were determined by PCR amplification with T7 bacteriophage vector arm specific primers. Human erythrocyte membranes were prepared from whole blood by hypotonic lysis and spectrin was extracted with a low ionic strength buffer and purified by size exclusion chromatography. The protein was biotinylated, immobilized on streptavidin-coated magnetic beads and biopanned against the phage library. Bound phage were eluted and amplified in E coli for three additional rounds of biopanning to eliminate non-specific protein-protein interactions. The P falciparum cDNA inserts of interacting phage were sequenced and compared to the PlasmoDB database. One of the sequences was identified as a putative aminopeptidase (PFI1570c), which has a 30.7% homology to a human aspartyl aminopeptidase, an enzyme catalysing the release of N-terminal amino acids from a peptide. The parasite protein contains a putative transmembrane domain at the C terminal end and is larger than the human form, with an estimated molecular weight of 65 kD. Several features that are critical for enzyme activity are conserved in the P falciparum aminopeptidase. These include twelve amino acids (four histidine, three glutamic acid and five aspartic acid residues), which are involved in the binding of catalytic zinc ions in the active site, as well as a putative N-myristoylation site and phosphorylation sites for casein kinase II and protein kinase C. Interestingly, the peptide fragment that bound to spectrin in the initial phage display screening, corresponds to a 33 amino acid fragment that is not found in the human aspartyl aminopeptidase. This suggests an evolutionary development of the parasite that allows the protease to bind to human spectrin. Mass spectrometry and microarray data from the PlasmoDB database indicate that the protein is present at the erythrocyte membrane and is expressed in all the developmental stages of the parasite’s erythrocytic life cycle. During the trophozoite stage the parasite modifies the erythrocyte membrane to allow transport of nutrients and waste products. The aminopeptidase could cleave spectrin and destabilise the membrane skeleton to facilitate the insertion of parasite protein channels during development. It may also play a role in proteolysis of the skeleton to enable the release of schizonts from infected erythrocytes.
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Turgeon, Nathalie, Marie-Josée Toulouse, Bruno Martel, Sylvain Moineau, and Caroline Duchaine. "Comparison of Five Bacteriophages as Models for Viral Aerosol Studies." Applied and Environmental Microbiology 80, no. 14 (May 2, 2014): 4242–50. http://dx.doi.org/10.1128/aem.00767-14.
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ABSTRACTBacteriophages are perceived to be good models for the study of airborne viruses because they are safe to use, some of them display structural features similar to those of human and animal viruses, and they are relatively easy to produce in large quantities. Yet, only a few studies have investigated them as models. It has previously been demonstrated that aerosolization, environmental conditions, and sampling conditions affect viral infectivity, but viral infectivity is virus dependent. Thus, several virus models are likely needed to study their general behavior in aerosols. The aim of this study was to compare the effects of aerosolization and sampling on the infectivity of five tail-less bacteriophages and two pathogenic viruses: MS2 (a single-stranded RNA [ssRNA] phage of theLeviviridaefamily), Φ6 (a segmented double-stranded RNA [dsRNA] phage of theCystoviridaefamily), ΦX174 (a single-stranded DNA [ssDNA] phage of theMicroviridaefamily), PM2 (a double-stranded DNA [dsDNA] phage of theCorticoviridaefamily), PR772 (a dsDNA phage of theTectiviridaefamily), human influenza A virus H1N1 (an ssRNA virus of theOrthomyxoviridaefamily), and the poultry virus Newcastle disease virus (NDV; an ssRNA virus of theParamyxoviridaefamily). Three nebulizers and two nebulization salt buffers (with or without organic fluid) were tested, as were two aerosol sampling devices, a liquid cyclone (SKC BioSampler) and a dry cyclone (National Institute for Occupational Safety and Health two-stage cyclone bioaerosol sampler). The presence of viruses in collected air samples was detected by culture and quantitative PCR (qPCR). Our results showed that these selected five phages behave differently when aerosolized and sampled. RNA phage MS2 and ssDNA phage ΦX174 were the most resistant to aerosolization and sampling. The presence of organic fluid in the nebulization buffer protected phages PR772 and Φ6 throughout the aerosolization and sampling with dry cyclones. In this experimental setup, the behavior of the influenza virus resembled that of phages PR772 and Φ6, while the behavior of NDV was closer to that of phages MS2 and ΦX174. These results provide critical information for the selection of appropriate phage models to mimic the behavior of specific human and animal viruses in aerosols.
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Cieślik, Martyna, Natalia Bagińska, Andrzej Górski, and Ewa Jończyk-Matysiak. "Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans." Microorganisms 9, no. 2 (January 20, 2021): 206. http://dx.doi.org/10.3390/microorganisms9020206.
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The authors emphasize how extremely important it is to highlight the role played by animal models in an attempt to determine possible phage interactions with the organism into which it was introduced as well as to determine the safety and effectiveness of phage therapy in vivo taking into account the individual conditions of a given organism and its physiology. Animal models in which phages are used make it possible, among other things, to evaluate the effective therapeutic dose and to choose the possible route of phage administration depending on the type of infection developed. These results cannot be applied in detail to the human body, but the knowledge gained from animal experiments is invaluable and very helpful. We would like to highlight how useful animal models may be for the possible effectiveness evaluation of phage therapy in the case of infections caused by gram-negative bacteria from the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) group of pathogens. In this review, we focus specifically on the data from the last few years.
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Shymialevich, Dziyana, Michał Wójcicki, Artur Wardaszka, Olga Świder, Barbara Sokołowska, and Stanisław Błażejak. "Application of Lytic Bacteriophages and Their Enzymes to Reduce Saprophytic Bacteria Isolated from Minimally Processed Plant-Based Food Products—In Vitro Studies." Viruses 15, no. 1 (December 20, 2022): 9. http://dx.doi.org/10.3390/v15010009.
Full textAbstract:
The aim of this study was to isolate phage enzymes and apply them in vitro for eradication of the dominant saprophytic bacteria isolated from minimally processed food. Four bacteriophages—two Enterobacter-specific and two Serratia-specific, which produce lytic enzymes—were used in this research. Two methods of phage enzyme isolation were tested, namely precipitation with acetone and ultracentrifugation. It was found that the number of virions could be increased almost 100 times due to the extension of the cultivation time (72 h). The amplification of phage particles and lytic proteins was dependent on the time of cultivation. Considering the influence of isolated enzymes on the growth kinetics of bacterial hosts, proteins isolated with acetone after 72-hour phage propagation exhibited the highest inhibitory effect. The reduction of bacteria count was dependent on the concentration of enzymes in the lysates. The obtained results indicate that phages and their lytic enzymes could be used in further research aiming at the improvement of microbiological quality and safety of minimally processed food products.
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Pathak-Vaidya, Prachitee, Surbhi Sharma, and Manasi Telang. "Bacteriophage as an antibacterial agent: a patent perspective." Future Microbiology 16, no. 17 (November 2021): 1327–39. http://dx.doi.org/10.2217/fmb-2021-0062.
Full textAbstract:
The present review encompasses a patent landscape on bacteriophage as an antimicrobial agent and one of the alternatives to combat antibiotic resistance in bacteria. This study gives a perspective on use of bacteriophages in various industries such as healthcare, food safety and animal and plant protection. Patenting activity was noted for all the antibiotic-resistant bacterial pathogens listed in the ‘critical’ category by the WHO. Broadly, claims of the analyzed patents were directed toward bacteriophage, composition/formulation containing phage, phage proteins and various methods of using or producing phage. The challenges to approval of phage therapy in clinical use may be overcome with the help of focused research and modification of the regulatory guidelines for phage therapy.
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Barbosa, Lidiane Nunes, André Felipe Berto de Almada, Jefferson Alessandro Schmitz Junior, Marco Aurélio Del Vechio, Karolaine Bezerra, Gabriela Favero Espolador, Mariana Carvalho dos Santos, et al. "Bacteriophages’ action against mastitis-causing bactéria." Research, Society and Development 9, no. 10 (September 22, 2020): e1849108541. http://dx.doi.org/10.33448/rsd-v9i10.8541.
Full textAbstract:
Mastitis is a breast tissue disease with a high incidence in dairy cows and implications ranging from the health of the animals to the economy of the sector. Although antibiotic therapy is widely used, the search for new perspectives in the management and treatment of this disease is necessary. Although phage research preceded the discovery of antibiotics, with the appearance of antibiotics and their efficiency in treating infections, phage therapy fell into disuse. However, phage therapy has now re-emerged as an alternative for combating multidrug-resistant bacteria. The relationship between phages, bacteria, and the immune system is unique, generating a wide range of opportunities, some of which have yet to be studied. Thus, the objective of this review was to analyze the use of bacteriophages in the control of bovine mastitis and its association with other natural products today. Phages have been shown to exert effective antibacterial and anti-biofilm activity, and their interactions with other substances of natural origin could be a viable path for treating disease. Despite being little explored, phages are already being considered as an alternative for treatment against the main bacterial agents of mastitis. In this review, the safety and future pathways of phage therapy are addressed in order to indicate points where research still needs to progress and the main advantages and difficulties in this area.
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Loponte, Rosa, Ugo Pagnini, Giuseppe Iovane, and Giuseppe Pisanelli. "Phage Therapy in Veterinary Medicine." Antibiotics 10, no. 4 (April 11, 2021): 421. http://dx.doi.org/10.3390/antibiotics10040421.
Full textAbstract:
To overcome the obstacle of antimicrobial resistance, researchers are investigating the use of phage therapy as an alternative and/or supplementation to antibiotics to treat and prevent infections both in humans and in animals. In the first part of this review, we describe the unique biological characteristics of bacteriophages and the crucial aspects influencing the success of phage therapy. However, despite their efficacy and safety, there is still no specific legislation that regulates their use. In the second part of this review, we describe the comprehensive research done in the past and recent years to address the use of phage therapy for the treatment and prevention of bacterial disease affecting domestic animals as an alternative to antibiotic treatments. While in farm animals, phage therapy efficacy perspectives have been widely studied in vitro and in vivo, especially for zoonoses and diseases linked to economic losses (such as mastitis), in pets, studies are still few and rather recent.