Phage Therapy: Going Temperate?

Temperate phages are highly abundant in bacterial genomes and are more readily available than lytic phages. While temperate phages are not seen as suitable for therapeutic purposes, their natural or engineered lytic variants hold promise. Advances in synthetic biology offer invaluable opportunities for the exploration of temperate phages in therapy, with the creation of lytic and tailored variants. Innovative approaches emerged exploring the integration of temperate phages in bacterial genomes for therapeutic purposes, as the dissemination of antibiotic susceptibility. Encouraging results have been reported from the use of temperate phages and their lytic variants in therapy, for example, reduced phage-resistant variants and endotoxin/toxin release; but negative outcomes have also been described – for example, increased sporulation. A cautious approach to temperate phage therapy is still required. Strictly lytic phages have been consensually preferred for phage therapy purposes. In contrast, temperate phages have been avoided due to an inherent capacity to mediate transfer of genes between bacteria by specialized transduction – an event that may increase bacterial virulence, for example, by promoting antibiotic resistance. Now, advances in sequencing technologies and synthetic biology are providing new opportunities to explore the use of temperate phages for therapy against bacterial infections. By doing so we can considerably expand our armamentarium against the escalating threat of antibiotic-resistant bacteria. Strictly lytic phages have been consensually preferred for phage therapy purposes. In contrast, temperate phages have been avoided due to an inherent capacity to mediate transfer of genes between bacteria by specialized transduction – an event that may increase bacterial virulence, for example, by promoting antibiotic resistance. Now, advances in sequencing technologies and synthetic biology are providing new opportunities to explore the use of temperate phages for therapy against bacterial infections. By doing so we can considerably expand our armamentarium against the escalating threat of antibiotic-resistant bacteria. one of two or more variants of a given gene that arises by mutation and is found in the same position on a chromosome. replacement of a native allele with an alternative one carrying a mutation, by homologous recombination. a virus that specifically infects and replicates within bacteria and archaea. microbial communities adhered to biotic or abiotic surfaces and embedded in a self-produced polymeric matrix. a prokaryotic version of adaptive immunity, in which DNA fragments of invading DNA are captured into CRISPR repeats, which allow for cleavage of the invader DNA by a Cas nuclease upon a second invasion. an allele whose phenotype masks the contribution of another allele of the same gene at the same locus. a phage-encoded enzyme, synthesized in the last stage of the phage lytic cycle, which cleaves the host cell wall for progeny release. a toxic molecule released from the cell wall of Gram-negative bacteria upon cell lysis. any organism with a complex nutritional requirement. a type of phage defined by its filament-like or rod-like shape, single-stranded DNA, and replication without host death. a molecular cloning method that allows the assembly of multiple DNA fragments in a single-tube isothermal reaction. the transfer of genetic material between organisms in the population other than by inheritance from ancestors (vertical transmission). the ability of a substance to trigger an immune response. a viral enzyme that catalyses the integration of viral DNA into the host chromosome. cell-wall-deficient variants of normally walled bacteria which retain the ability to grow and divide. a bacterial cell that harbours a prophage integrated into the chromosome or as a stable plasmid. a change in the properties of a bacterial cell caused by the presence of a prophage. a community of microorganisms that typically inhabit a particular environment, for example, the human gut. a general term used to describe modern (non-Sanger-based) high-throughput DNA sequencing. the ability of an organism to cause disease/damage in a host. a region of the chromosome of a pathogenic bacterium coding for virulence genes normally absent from nonpathogenic strains of the same/closely related species, acquired by horizontal transmission. the use of phages to treat bacterial infections. external pressure that defines whether an organism will be more or less successful at surviving in a given environment. blocking of a second phage infection superimposed on the previous one. the design and construction of new biological systems, organisms, or devices for useful purposes. the process by which a phage transfers genetic material, other than its own, from one bacterium to another. the severity or degree of damage caused by a pathogenic organism.