Phages - how do they work?

Bacteriophages, short form: phages (Greek: phagein = eat/swallow) are viruses in the wider biological sense. They exclusively attack bacteria and lyse them (“bacteria eaters”). Phages cannot reproduce alone by themselves, they require the bacterial cell as a host to reproduce within the host. A phage is much smaller than a bacterial cell and consists of its hereditary material (nucleic acid, mostly DNA) that is embedded in a protein envelope. This envelope is the “head” of the phage and has a crystalline shape that is only visible in an electron microscope. Additionally, a phage has a protein “tail” with a morphologically delicate fine structure at the end, for adsorption to the bacterial cell surface, the receptor. This receptor structure is so specific that a phage can only attack bacteria having a cell surface that exactly “matches”. After adsorption to the bacterial surface, the phage injects its nucleic acid into the bacterium that will now be forced to produce a new phage generation by using the bacterial enzyme equipment. One single bacterial cell produces such an enormous number of new phages that the pressure forces the bacterium to burst. The phages will immediately kill other bacteria with a surface matching with the phage. This effect is easily visible as lysis holes on densely grown bacterial layers.

As the number of young phages of a new phage generation is usually very high, the phages will quickly and completely attack bacteria in their proximity. This will happen as long as bacteria are available and receptors properly match.        
Among the giant numbers of bacterial cells at a certain habitat a statistical number of bacterial mutations can lead to phage-resistant bacteria. But, these will remain a minority and the phages will “co-evolve” and develop mutations that target the resistant bacteria. As a consequence, the phages will further be able to attack the bacteria. This phenomenon called “population dynamics” demonstrates in a simple manner what evolution of phages and their bacterial hosts in a habitat means. In natural environments, such a competition between bacteria and phages is mostly of scientific interest.

But, if the focus of interest is phage application or phage therapy in order to fight against a dense bacterial colonization, attention is drawn to these specific bacteria and a suitable phage: a special host-phage system. The “habitat” would not be garden soil or a water pit but a wound of the human body, an abscess, a chronic inflammation, a bacterial biofilm within the airways, an infected burn wound etc. In such cases, the bacterial numbers are often an extreme challenge for the human immune system that in the worst case collapses: antibiotics are the last possibility to fight against the bacteria.
There are many different kinds of antibiotics, they can be allocated to some well-defined chemical substance classes. Antibiotics are more or less specific against bacteria, but never specific for a certain bacterial species and even less against certain strains of a certain species. This is in contrast to phages that attack almost always only one bacterial species and more typically, only few strains of a species. This high specificity is typical for phages because of their biology: a phage-host system is like a key-lock function.

Therefore, phages are a completely different though biologically logic alternative to antibiotics: once a phage is found that attacks a pathogenic bacterium, the bacterium can be killed fast, specifically and without known side effects. The phage will leave other bacteria intact like the gut flora. After having lysed all target bacteria, the phage will decay and disappear, its components will be metabolized by the human body: when the bacterial number has decreased dramatically, the phage will be target of the reticulo-endothelian system: the therapeutic phage effect is “self-limiting”.     

While antibiotics are usually blocking bacteria during their fastest growth phase, phages are lysing bacteria independently of the growth phase.

As phages are the most abundant free living entities on earth (probably the tenfold number compared to bacteria), the human immune system knows phages from evolutionary history: we have a constant intake of phages via water, food and contact with natural materials, our gut flora contains enormous amounts of phages, like a complex ecosystem in balance.

This and the rather simple composition is probably the reason why phages are not known to cause allergic effects.