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Increasing antibiotic resistance numbers force both scientists and politicians to tackle the problem, and preferably without any delay. The application of bacteriophages as precision therapy to treat bacterial infections, phage therapy, has received increasing attention during the last two decades. While it looks like phage therapy is here to stay, there is still a lot to do. Medicine regulatory authorities are working to deliver clear instructions to carry out phage therapy. Physicians need to get more practical experience on treatments with phages. In this opinion article I try to place phage therapy in the context of the health care system and state that the use phages for precision treatments will require a seamless chain of events from the patient to the phage therapy laboratory to allow for the immediate application of phages therapeutically. It is not likely that phages will replace antibiotics, however, they will be valuable in the treatment of infections caused by multidrug resistant bacteria. Antibiotics will nevertheless remain the main treatment for a majority of infections.

Increasing antibiotic resistance numbers force both scientists and politicians to tackle the problem, and preferably without any delay. The application of bacteriophages as precision therapy to treat bacterial infections, phage therapy, has received increasing attention during the last two decades. While it looks like phage therapy is here to stay, there is still a lot to do. Medicine regulatory authorities are working to deliver clear instructions to carry out phage therapy. Physicians need to get more practical experience on treatments with phages. In this opinion article I try to place phage therapy in the context of the health care system and state that the use phages for precision treatments will require a seamless chain of events from the patient to the phage therapy laboratory to allow for the immediate application of phages therapeutically. It is not likely that phages will replace antibiotics, however, they will be valuable in the treatment of infections caused by multidrug resistant bacteria. Antibiotics will nevertheless remain the main treatment for a majority of infections. ; Peer reviewed

Bacteriophages of methanotrophic bacteria have been found in 16 out of 88 studied samples (underground waters, pond water, soil, gas and oil installation waters, fermentor cultural fluids, bacterial paste, and rumen of cattle) taken in different geographic zones of the Soviet Union. Altogether, 23 phage strains were isolated: 10 strains that specifically lysed only Methylosinus sporium strains, 2 strains that each lysed 1 of 5 Methylosinus trichosporium strains studied, and 11 strains that lysed Flavobacterium gasotypicum and, at the same time, 1 M. sporium strain. By fine structure, the phages were divided into two types (with very short or long noncontractile tails); by host range and serological properties, they fell into three types. One-step growth characteristics of the phages differed only slightly; the latent period varied from 6 to 8 h, the rise period varied from 4 to 6 h, and the average burst size was 100. All phages had guanine- and cytosine-rich double-stranded deoxyribonucleic acid consisting of common nitrogen bases. The molecular mass of the deoxyribonucleic acid as determined by restriction endonuclease analysis was 29.4 X 10(6) for M. sporium phages and 44 X 10(6) for F. gasotypicum phages. By all of the above-mentioned properties, all phages within each of the groups were completely identical to one another, but differed from phages of other groups. Bacteriophages lysing M. sporium and M. trichosporium GB2 were identical to phages M1 and M4, respectively, which were isolated earlier in the German Democratic Republic on the same methanotrophic species.

The excessive and improper use of antibiotics has led to an increasing incidence of bacterial resistance. In Europe the yearly number of infections caused by multidrug resistant bacteria is more than 400.000, each year resulting in 25.000 attributable deaths. Few new antibiotics are in the pipeline of the pharmaceutical industry. Early in the 20th century, bacteriophages were described as entities that can control bacterial populations. Although bacteriophage therapy was developed and practiced in Europe and the former Soviet republics, the use of bacteriophages in clinical setting was neglected in Western Europe since the introduction of traditional antibiotics. Given the worldwide antibiotic crisis there is now a growing interest in making bacteriophage therapy available for use in modern western medicine. Despite the growing interest, access to bacteriophage therapy remains highly problematic. In this paper, we argue that the current state of affairs is morally unacceptable and that all stakeholders ( pharmaceutical industry, competent authorities, lawmakers, regulators, and politicians) have the moral duty and the shared responsibility towards making bacteriophage therapy urgently available for all patients in need.

Exploring the possibilities of bacteriophages for tuberculosis
Bacteriophages have long offered prospects for treating bacterial infections. Is it time to use phages to control tuberculosis? Professor Graham F. Hatfull explores this. Bacteriophages – phages for short – are viruses that infect bacteria. They were discovered about 100 years ago and are prevalent throughout the biosphere and indeed throughout our bodies. Phages infect and kill bacteria as they replicate, and because of this antibacterial action, they have long been recognized as having therapeutic potential. This potential was largely side-lined once broad-acting antibiotics were discovered, but the troubling emergence of antimicrobial drug resistance has prompted the revisitation of bacteriophage therapeutics.

The concerning spread of antibiotic resistant bacteria has directed the spotlight upon bacteriophages, in short phages, as potential candidates for therapeutic purposes. Far for being a novelty, phage therapy has been widely used in the 20s and 30s in western countries until the discovery of antibiotics, which, coupled with a lack of knowledge of phage biology at that time, let to the replacement of phage therapy by antibiotics. On the other side of the planet, the Georgian Eliava Institute has been using phages for treating bacterial diseases since short after phage discovery a century ago. Georgian pharmacies commonly sell phage cocktails from the Institute without the need of a doctor's prescription. A thorough characterisation of the cocktail is though required for it to be accepted as pharmaceutical in the European Union. The potential to investigate the genetic material of microbial communities directly from the environment through metagenomics, allows for genomic characterisation of these cocktail. Furthermore, metagenomics analyses may lead to the discovery of novel phages with therapeutic potential, opening up a promising new horizon for phage therapy. This thesis is divided into five parts, each assigned a chapter. Chapter 1 provides the reader with an introduction to phage biology, history and metagenomics. Here, the main bioinformatics methods used throughout the studies of the following chapters are also presented and briefly described. Chapter 2 presents the paper "HostPhinder: A Phage Host Prediction Tool" published in May 2016. The tool predicts the bacterial host of a given phage based on co-occurrent k-mers between a query sequence and reference phage genomes with known host. HostPhinder's accuracy in predicting the host species and genus of an evaluation set was higher than 74% and 81%, respectively. The tool can be applied to identify the host of phage sequences found for instance in metagenomes allowing for a first step characterisation. Chapter 3 presents the paper "Metagenomic analysis of therapeutic PYO phage cocktails from 1997 to 2014" submitted in October 2017 and currently under peer-revision. In this study, the compositions of 3 batches of a Georgian cocktail from 1997 to 2014 was compared by means of Next Generation Sequencing (NGS) and metagenomic analysis. Thirty and 29 phage draft genomes were found in the cocktails from 1997 and 2014, respectively. One of them was present in both sample and did not resemble any known phage genomes, strongly suggesting its novelty. Phage representatives of all bacterial targets supposedly targeted by the cocktail's were found, as predicted using HostPhinder. A comparison between cocktails from 1997, 2000, and 2014 showed a closer composition between the first two cocktails. Chapter 4 presents the characterisation of historicalS. aureus phages, once used for phage typing. Finally, the conclusive Chapter 5, recapitulates the main findings of this thesis and frame them into the perspective of potential future investigations.

Bacteriophages (phages), natural enemies of bacteria, can encode enzymes able to degrade polymeric substances. These substances can be found in the bacterial cell surface, such as polysaccharides, or are produced by bacteria when they are living in biofilm communities, the most common bacterial lifestyle. Consequently, phages with depolymerase activity have a facilitated access to the host receptors, by degrading the capsular polysaccharides, and are believed to have a better performance against bacterial biofilms, since the degradation of extracellular polymeric substances by depolymerases might facilitate the access of phages to the cells within different biofilm layers. Since the diversity of phage depolymerases is not yet fully explored, this is the first review gathering information about all the depolymerases encoded by fully sequenced phages. Overall, in this study, 160 putative depolymerases, including sialidases, levanases, xylosidases, dextranases, hyaluronidases, peptidases as well as pectate/pectin lyases, were found in 143 phages (43 Myoviridae, 47 Siphoviridae, 37 Podoviridae, and 16 unclassified) infecting 24 genera of bacteria. We further provide information about the main applications of phage depolymerases, which can comprise areas as diverse as medical, chemical, or food-processing industry. ; DPP acknowledges the financial support from the Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BD/76440/2011. SS is an FCT investigator (IF/01413/2013). The authors also thank FCT for the Strategic Project of the UID/BIO/04469/2013 unit, FCT and European Union funds (FEDER/COMPETE) for the project RECI/BBB-EBI/0179/2012 ...

This article focuses on how bacteriophages (phages), antibiotic-resistance genes (ARGs), and disinfection practices intersect. Phages are considered to be the most abundant biological entities on Earth and they have the potential to transfer genes (including ARGs) among their bacterial hosts. In the urban water cycle, phages are used as indicators of fecal pollution and surrogates for human viral pathogens but they are also known to withstand common disinfection treatments deployed to produce safe drinking/reclaimed water. Recent studies also suggest that phages have the potential to become an additional footprint to monitor water safety. A precautionary approach should therefore include phages in surveillance programs aimed at monitoring antimicrobial resistance (AMR) in the urban water cycle. This article argues that phages ought to be used to assess the efficiency of disinfection treatments (both classical and novel) on reducing the risk associated with antibiotic resistance. Finally, this article discusses contributions to the advancement of AMR stewardship in aquatic settings and is relevant for researchers and water industry practitioners ; This work was supported by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement no. 792686, acronym ENVIROSTOME. This work was also supported by the Generalitat de Catalunya (ICRA-ENV 2017 SGR 1124) and by a New Lecturer Research Grant from the Society for Applied Microbiology. The authors are grateful for valuable contributions shared by BlueTech Research. ICRA researchers acknowledge the support for scientific equipment given by the European Regional Development Fund (FEDER) under the Catalan FEDER Operative Program 2007-2013 and by MINECO according to DA3ª of the Catalan Statute of Autonomy and to PGE-2010 as well as the funding from the CERCA program of the Catalan government.

The original publication is available at www.springerlink.com ; Bacteriophages infecting Staphylococcus epidermidis were isolated by mitomycin C induction. Three distinct phages (vB-SepiS-phiIPLA5, vB-SepiS-phiIPLA6, and vB-SepiS-phiIPLA7)-defined by plaque morphology, structure, virion proteins pattern, DNA restriction bands, and host range-were obtained. One-step growth curves of bacteriophages under optimal growth conditions for S. epidermidis F12 revealed eclipse and latent periods of 5-10 and 10-15 min, respectively, with burst sizes of about 5 to 30 PFU per infected cell. Transmission electron microscopy revealed that the phages were of similar size and belonged to the Siphoviridae family. Phage phi-IPLA7 had the broadest host range infecting 21 out of 65 S. epidermidis isolates. Phage phi-IPLA5 seemed to be a virulent phage probably derived from phi-IPLA6. Phages phi-IPLA5 and phi-IPLA7 exhibited increasing plaques surrounded by a halo that could be indicative of a polysaccharide depolymerase activity. Viable counts, determined during the infection of S. epidermidis F12, confirmed that phi-IPLA5 had a potent lytic capability and reduced S. epidermidis population by 5.67 log units in 8 h of incubation; in the presence of the mixture of phi-IPLA6 and phi-IPLA7, however, a reduction of 2.27 log units was detected © 2010 Springer Science+Business Media, LLC. ; This research study was supported by grants AGL2009-13144-C02-01 from the Ministry of Education of Spain and IB08-052 from FICYT (Regional Government of Asturias). P.G. was a fellow of the Spanish Ministry of Education Ramón y Cajal Research Programme. ; Peer Reviewed

ABSTRACTThe Application of bacteriophages as tracers in various aquatic systems is described with examples of three specific applications in the South West Water Authority area.The first two examples illustrate the use of bacteriophage for leak detection of a sewer and an impounding dam. The third example compares bacteriophage with fluorescein for the determination of time of travel in a river.

21 pages, 2 figures, 2 tables.-- This is an open access article distributed under the Creative Commons Attribution License ; The present work describes LC-ESI-MS/MS MS (liquid chromatography-electrospray ionization-tandem mass spectrometry) analyses of tryptic digestion peptides from phages that infect mastitis-causing Staphylococcus aureus isolated from dairy products. A total of 1933 nonredundant peptides belonging to 1282 proteins were identified and analyzed. Among them, 79 staphylococcal peptides from phages were confirmed. These peptides belong to proteins such as phage repressors, structural phage proteins, uncharacterized phage proteins and complement inhibitors. Moreover, eighteen of the phage origin peptides found were specific to S. aureus strains. These diagnostic peptides could be useful for the identification and characterization of S. aureus strains that cause mastitis. Furthermore, a study of bacteriophage phylogeny and the relationship among the identified phage peptides and the bacteria they infect was also performed. The results show the specific peptides that are present in closely related phages and the existing links between bacteriophage phylogeny and the respective Staphylococcus spp. infected ; This work received financial support from the Xunta de Galicia and the European Union (European Social Fund-ESF), from the Spanish Ministry of Economy and Competitivity Project AGL 2.013-48.244-R and from the European Regional Development Fund (ERDF) (2007–2013). This work was also supported by the GAIN-Xunta de Galicia Project (IN607D 2017/01) and the Spanish AEI/EU-FEDER PID2019-103845RB-C21 project. Mónica Carrera was supported by the Ramón y Cajal contract (Ministry of Science and Innovation of Spain) ; Peer reviewed

Zoonoses are infectious diseases transmitted directly or indirectly between animals and humans. Several important zoonotic pathogens colonize farm animals asymptomatically, which may lead to contamination of the food chain and public health hazards. Moreover, routine sampling of carcasses at retail by government authorities over the past 20 years suggests the prevalence of antibiotic resistance in foodborne pathogens has increased. If this continues, antibiotics may be ineffective against such pathogens in the future and alternative approaches, such as phage therapy, may be necessary. Intensive livestock farming is the only realistic way of meeting the demand for meat from an increasing global population and growth in middle class consumers in developing countries, particularly in Asia. This review elaborates on the use of phages to control zoonotic pathogens in intensively-reared livestock (poultry and pigs).

Bacteriophages: Nature's remedy for tackling superbugs and antimicrobial resistance
Given the increasing threat of antimicrobial resistance, Gunther Vanwezer, CEO of Vésale Bioscience, explains how bacteriophages offer a promising natural solution and outlines the company's efforts to become a pioneer in the development of innovative, personalised and sustainable phage-based therapy solutions. Antimicrobial resistance (AMR) is a major problem and an enormous public health challenge. According to the World Health Organization (WHO), AMR is one of the top ten global threats to public health. The projections are deeply concerning; AMR, often referred to as the "silent pandemic", is responsible for approximately 1.3 million deaths worldwide annually, with an alarming possibility of escalating to ten million deaths by 2050. The exponential growth of resistance to various antimicrobial products adds to the gravity of the situation. The effectiveness of treatments for bacterial infections is becoming increasingly problematic, and the search for new antibiotics is facing a significant decline. Bacteriophages appear to be the most promising natural solution in this worrying situation. Voted Europe's most innovative life sciences start-up in 2021, Vésale Bioscience is committed to developing personalised phage-based therapies to combat multi-resistant bacterial infections. In January 2023, the European Innovation Council (EIC) awarded it 1.8 million euros to encourage its research.