Phage banks as potential tools to rapidly and cost-effectively manage antimicrobial resistance in the developing world.

Lower and middle-income countries seldom develop vaccines and therapeutics for their own populations and are dependent on supplies from industrialized countries, which are often hampered by financial or supply chain limitations. This has resulted in major delays in delivery with significant loss of life, as seen with the coronavirus pandemic. Since the vast majority of deaths from the antimicrobial resistance crisis are expected to occur in developing countries, there is an urgent need for in-country production of antibacterial therapies such as phages. Nationally controlled phage banks might provide such a solution since locally developed phage therapies tailored to endemic bacterial strains could offer cost-effective antibiotic alternatives.

Preclinical data and safety assessment of phage therapy in humans.

Bacteriophages (phages) are natural biological entities that kill bacteria with species specific precision, rendering them attractive for therapeutic purposes. Phages were discovered over a century ago, but, after antibiotic discovery, their use as antimicrobials dwindled. Interest in phage therapy has, however, been rekindled by increasing multi-drug resistance to routine and frontline antibiotics and by the slowing of antibiotic innovations. To build on fundamental phage research studies and compassionate usage, information on safety and efficacy of phages is needed to motivate clinical trials and are necessary for phage therapy to become mainstream. In this review, we discussed essential phage characterisation parameters alongside the merits and limitations of state-of-the-art models to gather preclinical data on the safety and efficacy of phage therapeutics.

Low activity of lytic pelagiphages in coastal marine waters.

Phages infect marine bacteria impacting their dynamics, diversity and physiology, but little is known about specific phage-host interactions in situ. We analyzed the joint dynamics in the abundance of phage-related transcripts, as an indicator of viral lytic activity, and their potential hosts using a metatranscriptomic dataset obtained over 2 years in coastal temperate waters of the NE Atlantic. Substantial temporal variability was identified in the expression levels of different phages, likely in response to host availability. Indeed, a significant positive relationship between the abundance of transcripts from some of the most abundant phage types (infecting SAR11, SAR116 and cyanobacteria) and their putative hosts was found. Yet, the ratio of increase in phage transcripts per host cell was significantly lower for pelagiphages than for the HMO-2011 phage, which infects SAR116. Despite the high abundance of pelagiphages in the ocean, they may be less active than other phage types in coastal waters.

Bacteriophage behavioral ecology: How phages alter their bacterial host's habits.

Bacteriophages have an essential gene kit that enables their invasion, replication, and production. In addition to this "core" genome, they can carry "accessory" genes that dramatically impact bacterial biology, and presumably boost their own success. The content of phage genomes continue to surprise us by revealing new ways that viruses impact bacterial biology. The genome of a Clostridium difficile myovirus, phiCDHM1, contains homologs of three bacterial accessory gene regulator (agr) genes. The agr system is a type of quorum sensing (QS), via which the phage may modify C. difficile interactions with its environment. Although their mechanism of action is unknown, mutants in bacterial versions of these genes impact sporulation and virulence. To explore how phage QS genes may influence C. difficile biology, we examine the main categories of bacterial behavior that phages have been shown to influence and discuss how interactions via QS could influence behavior at a wider level.

Phages in nature.

Bacteriophages or phages are the most abundant organisms in the biosphere and they are a ubiquitous feature of prokaryotic existence. A bacteriophage is a virus which infects a bacterium. Archaea are also infected by viruses, whether these should be referred to as 'phages' is debatable, but they are included as such in the scope this article. Phages have been of interest to scientists as tools to understand fundamental molecular biology, as vectors of horizontal gene transfer and drivers of bacterial evolution, as sources of diagnostic and genetic tools and as novel therapeutic agents. Unraveling the biology of phages and their relationship with their hosts is key to understanding microbial systems and their exploitation. In this article we describe the roles of phages in different host systems and show how modeling, microscopy, isolation, genomic and metagenomic based approaches have come together to provide unparalleled insights into these small but vital constituents of the microbial world.