Phages: from biology to the clinic

Multidrug-resistant pathogens have become increasingly common in hospital settings. Here, the authors investigate the efficacy of adjunctive antibiotic and phage therapy in a human cell model and a murine model of ventilator-associated pneumonia.

The bacterial anti-phage defense systems known as ‘Zorya’ consist of a membrane protein complex (ZorAB) and soluble components of unclear function. Here, the authors solve cryo-EM structures of the ZorAB complex and show that the soluble component ZorE displays nickase activity and acts as an effector module.

Two distinct phage engineering strategies—mutating phage genes targeted by bacterial anti-phage systems and arming phages with genes that counteract these systems—have enabled the circumvention of bacterial anti-phage defenses.

Toxin-antitoxin systems make up a branch of the bacterial anti-phage immune system. Here, Johannesman et al demonstrate that some phages have co-opted an orphan antitoxin to counter a DNA ADP-ribosyltransferase defense system.

Structures of Shigella bacteriophage Sf14 show similarity with several features from diverse bacteriophages that, when combined, produce a T = 9 icosahedral capsid coated in decoration proteins and a contractile tail with two tail fibers.

During urinary tract infections, the urinary microbiome is enriched in temperate phages with increased recombination activity, possibly facilitating bacterial infections. Temperate phages could be used as therapeutic “Trojan Horses”.

Phage VAC3 adaptations to the mucosal environment (improved replication in mucin-treated hosts and retention in the respiratory tract) are mechanisms that can exploited as prophylactic measure to protect mice from a lethal dose of P. aeruginosa.

The application of phage therapy for multidrug-resistant infections is mainly limited to personalized therapy due to the narrow host range of individual phages. Here, Kim et al. identify groups of phages that use non-redundant receptors, and present a blueprint for the development of effective, broad-spectrum phage-antibiotic combinations.

Retrons are bacterial genetic elements that, in combination with toxic effector proteins, can serve as antiphage defense systems. Here, the authors show that some phages can evade retrons and other defense systems by expressing specific tRNAs.

A catalog of phages associated with Sulfurimonas reveals unexplored diversity and potential viral impacts, providing new insight into the phage-host coevolution.

Here, the authors profile the gut phageome of individuals recruited into two double-blind randomized trials of Fecal Microbial Transplantation for ulcerative colitis, showing that phage communities are stable in health, dysbiotic in ulcerative colitis, modulated by antibiotics and by fecal transplants, with one Oscillospiraceae phage being associated with disease remission.

The study reveals that the Southern Ocean hosts a unique and largely underexplored DNA viral community. It explores the diversity of viral communities infecting all domains of life and their seasonality, emphasizing their role in ecosystem dynamics.

Gp1, a 58-amino acid DNA-binding protein encoded by betatectivirus GIL01, is responsible for maintenance of the GIL01 linear prophage genome in host Bacillus thuringiensis serovar israelensis.

Six roseophages that infect Roseobacter RCA are described as new Occultatumvirinae, to which further 232 marine uncultivated virus genomes obtained from environmental genome datasets could be assigned; these are globally distributed in 11 subgroups.

Leveraging bioinformatics, proteomics, and cryogenic electron microscopy, this study deciphers the architecture and design principles of the therapeutic Pseudomonas phage Pa193.

Phage therapy often relies on labour-intensive and time-consuming methods that could lead to delays in medical treatment. Here, authors describe an all-in-one solution for navigating multiple, large, decentralized biobanks, allowing for rapid high-throughput phage susceptibility testing.

The SPP1 tail completion protein, representative of a widespread family of essential phage proteins, is shown to play a role in capsid-tail attachment and to be essential for routing of phage DNA from the viral particle to the bacterial cytoplasm.

Bacteriophage strain DS6A efficiently eradicates intracellular Mtb in human macrophages, while humanized mice treated with DS6A show improved pulmonary function and reduced Mtb load in mouse organs with greater efficacy in the spleen.

In this work, authors utilise a pan-resistant Pseudomonas aeruginosa in vivo infection model to demonstrate antibiotic re-sensitisation with bacteriophage therapy.