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As pathogenic bacteria continue to develop multi-drug resistance, antibacterial treatment strategies such as bacteriophages are needed. This book serves as a brief yet exhaustive guide to the biology of bacteriophages and their role in health and disease. It is a useful resource for microbiologists, bacteriophage researchers, clinicians providing bacteriophage therapy, and dental and medical students.

Bacteriophages.

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Since the late 1800s, the discovery of new viruses was a gradual process. Viruses were described one by one using a suite of techniques such as (electron) microscopy and viral culture. Investigators were usually interested in a disease state within an organism, and expeditions in viral ecology were rare. The advent of metagenomics using high-throughput sequencing has revolutionized not only the rate of virus discovery, but also the nature of the discoveries. For example, the viral ecology and etiology of many human diseases are being characterized, non-pathogenic viral commensals are ubiquitous, and the description of environmental viromes is making progress. This Frontiers in Virology Research Topic showcases how metagenomic and bioinformatic approaches have been combined to discover, classify and characterize novel viruses.

virome --- biological dark matter --- metagenome --- metagenomics --- bacteriophages --- bioinformatics --- virus discovery --- phages

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In the context of disease pathogenesis, it has been observed that after inadequate administration of antibiotics, animals become more susceptible to intestinal colonization and organ invasion by enteropathogens, these could be related to changes caused in the gastrointestinal microbial community. Therefore, we must reconsider the negative consequences that disruption of the microbiome has in the biology of metazoans (dysbacteriosis). Alternations of the intestinal microbiota composition in animals can be caused by multiple factors, including the misuse of antibiotics, having as a result a negative impact on the development and function of the immune, endocrine, nervous, and digestive systems. For this reason, social concerns regarding the development of antibiotic-resistant microorganisms have resulted in an urgent necessity to find feasible alternatives to maintain animal health and performance without the use of antibiotic growth promoters (AGP), in order to sustain livestock production as an economically viable source of food for human consumption. Hence, research about AGP alternatives such as probiotics, prebiotics, phytochemicals, organic acids, enzymes, and vaccines has become a priority for many scientists around the world.

Bacteriophages. --- Food contamination. --- Gastrointestinal system --- Microbiology. --- Feed additives --- Antibiotics --- Livestock --- Antimicrobial resistance --- Microbiome

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There is talk of an upcoming antibiotic armageddon, with untreatable post-operative infections, and similarly untreatable complications after chemotherapy. Indeed, the now famous “O’Neill Report” (https://amr-review.org/) suggests that, by 2050, more people might die from antibiotic-resistant bacterial infections than from cancer. While we are still learning all the subtle drivers of antibiotic resistance, it seems increasingly clear that we need to take a “one health” approach, curtailing the use of antibiotics in both human and veterinary medicine. However, there are no new classes of antibiotics on our horizon. Maybe something that has been around “forever” can come to our rescue—bacteriophages! Nevertheless, it is also necessary to do things differently, and use these new antimicrobials appropriately. Therefore, an in-depth study of bacteriophage biology and case-by-case applications might be required. Whilst by no means comprehensive, this book does cover some of the many topics related to bacteriophages as antimicrobials, including their use in human therapy and aquaculture. It also explores the potential use of phage endolysins as substitutes of antibiotics in two sectors where there is an urgent need—human therapy and the agro-food industry. Last but not least, there is an excellent perspective article on phage therapy implementation.

bacteriophages --- dairy industry --- pathogens --- lactic acid bacteria --- fermentation failure --- biofilms --- antimicrobial resistance --- antimicrobials --- lysins --- horizontal gene transfer, transduction --- biofilm --- phage therapy --- resistance --- bacteriophage --- models --- agent based --- mass action --- bacterial phage resistance --- regression modeling --- MRSA --- Clostridium difficile --- Clostridium difficile infection --- microbiome --- in vitro fermentation model --- marine vibrios --- biological control --- aquaculture --- interactions --- vibriosis --- Aeromonas hydrophila --- Motile Aeromonas Septicemia --- MAS --- multiple-antibiotic-resistance --- striped catfish (Pangasianodon hypophthalmus) --- endolysin --- antibiotics --- one health --- protein engineering --- Aeromonas salmonicida --- furunculosis --- phage-resistant mutants --- proteins --- infrared spectroscopy --- lysin --- lytic enzyme --- peptidoglycan hydrolase --- antimicrobial --- antibacterial --- antibiotic resistance --- bacteriophage therapy --- Nagoya Protocol --- CRISPR CAS --- phage isolation --- phage resistance --- Staphylococcus --- Kayvirus --- Vibrio anguillarum --- fish larvae --- challenge trials --- phage display --- enzybiotics --- Bacteriophages --- diabetic foot ulcer --- osteomyelitis --- Staphylococcus aureus --- Antibiotic-resistant bacteria --- lysogenic conversion --- prophage induction --- read recruitment --- shiga toxin --- American Foulbrood --- phage --- Paenibacillus larvae --- Brevibacillus laterosporus --- treatment --- safety --- bystander phage therapy --- Mycobacterium smegmatis --- mycobacteriophages --- directed evolution --- PlyC CHAP --- protein net charge --- CBD-independent --- FoldX --- STEC-specific bacteriophage --- whole genome sequencing --- STEC O145 strains --- antimicrobial agent --- Pseudomonas aeruginosa --- dual-species --- antibiotic --- synergy --- simultaneous --- sequential --- microbiome therapy --- evolution

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Phages have shown a high biotechnological potential with numerous applications. The advent of high-resolution microscopy techniques aligned with omic and molecular tools have revealed innovative phage features and enabled new processes that can be further exploited for biotechnological applications in a wide variety of fields. The high-quality original articles and reviews presented in this Special Issue demonstrate the incredible potential of phages and their derived proteins in a wide range of biotechnological applications for human benefit. Considering the emergence of amazing new available bioengineering tools and the high abundance of phages and the multitude of phage proteins yet to be discovered and studied, we believe that the upcoming years will present us with many more fascinating and new previously unimagined phage-based biotechnological applications.

toxicity --- encapsulation --- n/a --- cancerous tumors --- bacteriophage-derived lytic enzyme --- native gel electrophoresis --- bacteriophages --- Cpl-1 --- O-antigen --- ESKAPE --- Clostridium perfringens --- X-ray crystallography --- macromolecular interactions --- safety --- biofilm --- major coat protein --- Streptococcus agalactiae --- Staphylococcus aureus --- tail sheath protein --- magnetic separation --- serotyping --- pathogenic viruses --- liposomes --- tuberculosis --- Listeria monocytogenes --- nanotubular structures --- alpha-sheet --- biosensors --- sarcoidosis --- tailspike proteins --- M13 bacteriophage --- Streptococcus pneumoniae --- gene expression regulation --- bacteriophage recombination --- self-assembly --- phage therapy --- R-type pyocin --- contractile injection systems --- bacteriophage vB_EcoM_FV3 --- microtiter plate assay --- Enterococcus faecalis --- culture enrichment --- drug delivery vehicles --- neurodegenerative disease --- landscape phage --- niosomes --- bacteriophage --- Myoviridae --- bacteriophage evolution --- porous structure --- phage-host interaction --- phage display --- immune response --- antibiotic resistance --- Pseudomonas aeruginosa --- phage --- bacteriocin --- Appelmans --- fluorescence sensor --- molecular probe --- nanomedicine --- Shigella flexneri --- reporter phage --- filters --- in vitro activity --- capsid dynamics --- immunoscreening --- diagnostics --- microarray --- receptor-binding protein --- endolysin --- enzybiotics --- transfersomes --- T7phage library --- Pal