The recurrence of an infection after antibiotic therapy is often caused not only by drug resistance but by a specific state of bacteria that makes them temporarily “immune” to medication. According to a recent discovery by the Hebrew University of Jerusalem, microbes choose two different “shutdown modes” to protect themselves from drugs, allowing them to trigger a new wave of infection after the threat has passed.
A Dual Survival Strategy
The fundamental principle of antibiotics is to destroy bacteria that are in an active growth phase. However, a small group of “persistent” cells manages to survive the attack, ultimately leading to a recurrence of the infection. For decades, it was believed that uniform “dormancy” was behind this phenomenon. However, the work of Professor Nathalie Balaban and Adi Rotem has fundamentally changed this view.
“We discovered that bacteria choose two radically different biological paths to protect themselves from antibiotics,” explains Professor Balaban. “Understanding the fundamental difference between these strategies helps us resolve years of contradictory data and develop far more effective, targeted treatment methods.”
1. “Strategic Hibernation”
In the study, researchers examined the behavior of E. coli under conditions of natural starvation. It was established that the gradual depletion of nutritional resources forces the bacteria to enter a strictly regulated phase of growth arrest. During this time, the cell undergoes a fundamental transformation:
Metabolic Conservation: The metabolic rate is reduced to a minimum, helping the cell maximize the conservation of vital energy.
Resource Optimization: The bacteria shut down energy-intensive biological mechanisms, including flagellar motility, chemotaxis, and ribosome biogenesis.
Structural Resilience: The cell acquires spore-like stability, making it extremely resistant to environmental stress and antibiotics (such as ampicillin).
The main characteristic of this mode is predictability and synchronicity. Although the bacteria meet the antibiotic attack in a state of inactivity, they “wake up” immediately and simultaneously as soon as nutrients are restored, leading to a rapid recurrence of the infection.
2. Disrupted Mode: Biological Chaos
In cases where environmental conditions change suddenly and sharply (for example, under the influence of chemical stressors), the bacteria do not have time to activate adaptive mechanisms and enter a phase of “disrupted growth arrest.” During this time, the cell loses control over its own homeostasis:
Genetic and Phenotypic Heterogeneity: Cells within the population exhibit chaotic and unpredictable behavior. Unlike the regulated mode, cells here are in radically different biological states, creating high “genetic noise.”
Metabolic Dysfunction: Although cell growth and division are halted, they continue to consume energy intensely. High metabolic activity without growth leads to the irrational wasting of cellular resources and premature exhaustion of the bacteria.
Desynchronized Regeneration: The “awakening” process is extremely disorganized—some cells resume functioning within a few hours, while for others, returning to the reproductive phase takes several days.
This chaotic state is critical for the bacteria: membrane permeability increases, making them extremely vulnerable. It is this imbalance that creates a new therapeutic opportunity—bacteria in a disrupted mode become sensitive to targeted therapies that are completely harmless to healthy or stably dormant cells.
It is noteworthy that the significance of this discovery extends beyond microbiology. Scientists suggest that similar biological patterns may operate in cancer cells. Pathological cells may manage to resist chemotherapy through such strategic “self-shutdown,” which subsequently leads to a relapse of the disease.
Source: Science
