Bacteriophage

Bacteria are tiny single-celled organisms. Some of them make people sick. A bacteriophage is a tiny entity that attacks and kills exactly such bacteria. It is not itself a living organism in the usual sense, but a virus: a shell containing genetic information inside, which can only multiply inside a foreign cell. A bacteriophage cannot infect human cells; it is specialized in bacteria. The name comes from Greek and roughly means “bacteria eater”.

The hope against resistant germs

Medicine has been using antibiotics against bacterial infections for roughly eighty years. These are drugs that kill bacteria or prevent them from multiplying. The problem: bacteria change over generations and become insensitive to these agents. They are then called resistant. The World Health Organization ranks antibiotic resistance among the greatest health threats of all.

This is where phages come into play. They work on a completely different principle than antibiotics. A bacterium that is resistant to several antibiotics can still be destroyed by a matching phage. There are already individual documented cases in which patients with otherwise untreatable infections were saved this way.

A second advantage is precision. An antibiotic often hits many bacterial species at once, including the beneficial ones in the gut. A phage usually infects only a single species, or even just certain strains of it. This precision is at the same time the biggest drawback: one first has to find out which phage matches the patient’s pathogen.

How a phage hijacks a bacterium

Under the electron microscope, many phages look like a lunar landing module. They have an angular head, a tail, and fine little legs. The head contains the genetic material, i.e. the phage’s blueprint. It uses its little legs to probe the surface of a bacterium. If the surface fits like a key in a lock, it docks on.

The phage then injects its genetic material into the bacterium. The bacterium reads this foreign blueprint as if it were its own instruction. It starts building hundreds of copies of the phage instead of multiplying itself. Eventually the cell bursts, the new phages are released and go looking for the next bacteria. You can imagine this like a hijacked 3D printer that now only prints components for its attacker.

This results in an unusual property: the drug multiplies itself. As long as target bacteria are present, the number of phages grows. Once the bacteria are gone, the phages disappear again too. Incidentally, not all phages kill immediately. Some insert their genetic material into the bacterium and remain dormant for a long time. For therapies, one therefore specifically looks for the aggressive variants.

Phages in clinics, labs, and on the stock market

In Georgia and Poland, phages have been used as a regular therapy for decades. In Western Europe and the USA, they are not yet a normally approved medicine. There, they are mostly used only on a case-by-case basis when nothing else helps anymore. Several large clinical trials are underway, for example against chronic lung infections in cystic fibrosis.

In the business press, phages therefore appear as a topic for young biotech companies. Such companies build up libraries with thousands of phages and search among them for the right candidate for a pathogen. Software is also used in this search: programs compare genetic data from bacteria and phages and estimate in advance which combination is likely to work.

Outside of medicine, phages have been in use for longer. In the USA, phage sprays are permitted to be applied to food against salmonella and listeria. In basic research, phages are a standard tool: many genetic engineering methods trace back to insights gained from the battle between bacteria and their phages, including the CRISPR gene-editing tool.