Antibiotics play a pivotal role in treating bacterial infections, yet their effectiveness can sometimes falter, even when the bacteria are not resistant to the medication. A groundbreaking study by researchers at the University of Basel, published in Nature, challenges the prevailing belief that antibiotic therapy failures stem from a small subset of particularly resilient bacteria.
Challenging Conventional Views
Traditionally, scientists believed that a small group of dormant bacteria, known as persisters, were responsible for antibiotic therapy failures. These persisters can survive antibiotic treatment and later cause reinfections. However, a team led by Professor Dirk Bumann from the university’s Biozentrum has uncovered surprising new evidence.
“Contrary to the prevailing notion, antibiotic therapy failure is not due to a small number of persisters,” Bumann explains. “In fact, the majority of Salmonella bacteria in infected tissues are inherently difficult to eliminate. Our research suggests that standard laboratory tests can mislead us about the true nature of bacterial resilience.”
Nutrient Deprivation as the Culprit
The team studied the behavior of Salmonella in both mouse models and laboratory systems that mimic human tissue. They discovered that the body’s natural defense mechanism, which involves reducing nutrient availability, plays a key role in the bacteria’s resistance. Bumann elaborates: “When nutrients are scarce, bacteria grow very slowly. While this may seem beneficial, it actually hinders the efficacy of most antibiotics, which work more effectively on rapidly dividing bacteria.”
As a result, antibiotics are less potent, and reinfections can occur even after prolonged treatment. This novel understanding of how bacteria cope with antibiotics could dramatically shift the direction of future antibiotic research.
Real-Time Analysis Reveals the Truth
To gather their insights, the researchers employed an innovative technique to monitor antibiotic effects in individual bacteria in real time. Dr. Joseph Fanous, the study’s first author, explains their findings: “Our study demonstrates that almost the entire Salmonella population can survive antibiotic treatment for extended periods. This is not just a matter of a few super-resilient persisters.”
The research team also highlighted a critical flaw in traditional testing methods: their indirect and delayed assessment leads to inaccurate results. Fanous notes, “Standard laboratory tests underestimate bacterial survival rates and incorrectly indicate the presence of persisters that do not actually exist. This misconception has influenced research for many years.”
Implications for Antibiotic Research
This groundbreaking discovery could revolutionize antibiotics research. Professor Dirk Bumann underlines the importance of studying bacterial behavior “in real-time and under biologically relevant conditions.” He adds, “Methods like real-time single-cell analysis will likely become standard in the future.”
The shift from focusing on persister cells to understanding the impact of nutrient starvation could lead to more effective treatments. Bumann states, “This is a crucial step towards combating difficult infections.”
The research is part of the National Center of Competence in Research (NCCR) “AntiResist,” led by Dirk Bumann. The consortium aims to develop innovative strategies to fight bacterial infections.
Conclusion
Antibiotic resistance may be more of a challenge than previously thought. The University of Basel study exposes the erroneous focus on persisters and highlights nutrient starvation as a critical factor. By embracing advanced real-time analysis techniques, researchers can open new avenues for antibiotic development. As our understanding deepens, so does our potential to combat resistant bacteria effectively.
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Source:
Journal reference:
Fanous, J., et al. (2025). Limited impact of Salmonella stress and persisters on antibiotic clearance. Nature. doi.org/10.1038/s41586-024-08506-6.
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