1. The problem of “dormant” bacteria (persisters)

Why do bladder infections, lung infections, or inflammation around implants often return weeks after a successful course of antibiotics? The answer lies in the existence of persister cells.

What are persisters?

Unlike classic antibiotic resistance, in which the bacterium changes its genetic material to neutralize a drug, persisters represent a survival strategy through inactivity. These bacteria almost completely shut down their metabolism. Because antibiotics usually target processes that occur when bacteria grow or divide (e.g., cell wall synthesis), they have no point of attack in “dormant” cells.

Once antibiotic therapy ends and conditions in the body become favorable again, these cells “wake up,” and the infection flares up again. This is one of the main reasons why chronic infections are so difficult to treat.

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2. Bacteriophages: The hunters that never sleep

Bacteriophages (phages for short) are viruses that act as natural antagonists of bacteria. Unlike chemical agents, phages are biological entities that have specialized over billions of years in overcoming bacterial defense mechanisms.

The lytic cycle and persisters

Current research, as described on phage.help, shows that certain phages can attach to dormant bacteria. While an antibiotic waits for the bacterium to become active, the phage injects its genetic material even into inactive cells.

Some phages wait patiently inside the bacterium until it ramps up its metabolism again, then immediately take control and destroy the cell (lysis). Other phages produce enzymes that can directly attack the cell wall of the dormant bacterium.

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3. Excursus: Georgia’s legacy and the renaissance in the West

The use of phages is by no means new. In Georgia (Eliava Institute, Tbilisi), patients have been treated with phage cocktails for over 100 years. While the West largely abandoned phage research after the discovery of penicillin, the East perfected the isolation of phages from the environment.

Why we can learn from Georgia today

In Georgia, it is routine clinical practice to use phages against chronically infected wounds where Western antibiotics have failed. Physicians there have long known that phages are particularly effective in biofilms—those complex communities in which persister cells preferentially survive. This decades-long experience is now feeding into modern biotechnological research to develop standardized antibiotic resistance solutions for the global market.

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4. Scientific focus: Phage-antibiotic synergy (PAS)

A central pillar of modern phage therapy is the insight that phages and antibiotics, as a team, often produce an effect that goes far beyond the sum of their individual parts. We refer to this as phage-antibiotic synergy (PAS).

The PAS mechanism in detail

The synergy is based on several fascinating biological interactions:

1. Filamentation: Certain antibiotics (e.g., beta-lactams) at sublethal doses (doses that do not kill the bacterium immediately) stimulate bacteria to elongate without dividing. These enlarged surfaces provide phages with more space for receptors, massively increasing the infection rate and the number of phages produced within the bacterium.

2. Breaking up biofilms: Bacteria in biofilms are protected by a matrix of sugars and proteins. Phages produce depolymerases—enzymes that literally “eat away” at this biofilm. Once the matrix becomes porous, antibiotics that previously bounced off the surface can penetrate deep into the biofilm and kill the bacteria (including persisters).

3. The evolutionary dilemma: Bacteria that try to become resistant to phages often have to alter their surface structures. This change frequently causes them to lose their resistance to antibiotics. The bacterium faces a choice: either it dies from the phage, or it becomes susceptible to the antibiotic again.

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5. Why antibiotics alone often fail: The resistance crisis

The global rise in multidrug resistance is one of the greatest threats to modern medicine. Classic antibiotics have three key disadvantages:

• Low selectivity: They often kill beneficial bacteria as well (microbiome), leading to side effects and further health problems.

• Static effect: They cannot adapt. Once a bacterium has developed resistance, the antibiotic remains ineffective.

• Persister blindness: As mentioned at the outset, antibiotics do not “see” inactive cells.

Bacteriophage therapy addresses all three points: it is highly specific, phages co-evolve with their hosts, and they can eliminate dormant cells.

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6. From research to the clinic: The patient’s pathway

Although the benefits are obvious, access to phage therapy in Germany is still often challenging. At present, it is mostly used as an “individual treatment attempt” (under the Declaration of Helsinki) when all other options have been exhausted.

The phagogram as the key

To ensure successful therapy, a phagogram must first be created. In this process, the patient’s bacteria are brought together in the laboratory with various phages to see which phage kills the specific pathogen most effectively. This personalized approach is at the core of modern phage therapy.

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7. FAQ – Frequently asked questions

1. How do phages find dormant bacteria in the body? Phages move by diffusion and random collisions. Because they are extremely abundant and have highly specific receptors, they “recognize” their target bacteria by their surface structure, regardless of whether the bacterium is currently active or dormant.

2. Can I undergo phage therapy in addition to my antibiotics? Yes, this is often precisely the goal of phage-antibiotic synergy. The combination can significantly increase the chances of recovery. However, this should always be done under the guidance of a specialized physician.

3. Why do phages not kill my beneficial gut bacteria? Phages are specialists. A phage that kills a harmful Pseudomonas bacterium cannot infect a beneficial Lactobacillus in the gut. This is a decisive advantage over broad-spectrum antibiotics.

4. Where can I receive phage therapy? In Germany, there are specialized centers (e.g., in Berlin or Braunschweig) that use phages as part of studies or individual treatment attempts. Many patients also contact institutes in Belgium or Georgia. You can find more information on our treatment page.

5. Do phages also help against viruses such as COVID or influenza? No. Bacteriophages are viruses that infect bacteria only. They have no effect on human cells or other types of viruses.

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Conclusion: A biological weapon against time

The discovery that bacteriophages kill dormant bacteria is a turning point. It deprives the most dangerous pathogens of their most important hiding place. By making intelligent use of phage-antibiotic synergy and integrating historical insights from Eastern Europe into modern medicine, we can finally tackle chronic infections at their root.

Bacteriophage therapy is not only an alternative, but a necessary evolution in the fight against global antibiotic resistance. It is time we give these biological hunters the place in medicine that they deserve.

Interesting links for you:

• The power of bacteriophages – An overview

• What exactly are bacteriophages?

• Contact & advice in the expert forum

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Note: This article is for informational purposes and does not replace medical advice.