A new study from the University of Basel reveals nutrient starvation, not resilient “persisters,” as the key factor behind the failure of antibiotics against non-resistant bacteria. This revelation could reshape future treatments of bacterial infections.
Antibiotics are essential for treating bacterial infections, but their occasional ineffectiveness, even against non-resistant bacteria, has puzzled scientists for years. A new study from the University of Basel, published in the journal Nature, now shines light on this phenomenon, drastically altering our understanding of antibiotic failures.
The research, conducted by Dirk Bumann’s team at the Biozentrum of the University of Basel, counters the long-held belief that antibiotic therapy fails because of a small subset of dormant, resilient bacteria known as “persisters.” These persisters have been thought to survive antibiotic treatments, causing relapses later on.
“Contrary to widespread belief, antibiotic failure is not caused by a small subset of persisters. In fact, the majority of Salmonella in infected tissues are difficult to kill,” Bumann, a professor of infection biology, said in a news release.
The study underscores that standard lab tests have been misleading, painting a wrong picture of bacterial resilience.
The researchers used innovative real-time methods to study antibiotic action on single bacteria in both Salmonella-infected mice and tissue-mimicking lab models.
They found that nutrient starvation, a common bodily defense mechanism, significantly increases bacterial resilience. The shortage of nutrients causes bacteria to grow very slowly, making conventional antibiotics much less effective, because these drugs are designed to target faster-growing bacteria.
“Under nutrient-scarce conditions, bacteria grow very slowly,” added Bumann. “This may seem good at first but is actually a problem because most antibiotics only gradually kill slowly growing bacteria.”
This slow growth means that bacteria can linger and cause relapses even after prolonged therapy.
The misconception that a small group of hyper-resilient persisters are the primary culprits has steered research for decades.
“We demonstrated that nearly the entire Salmonella population survives antibiotic treatment for extended periods, not just a small subset of hyper-resilient persisters,” added first author Joseph Fanous.
Traditional lab tests have underestimated the number of surviving bacteria, leading to the misguided focus on persisters.
“Traditional tests underestimate the number of surviving bacteria,” Fanous added. “And they falsely suggest the presence of hyper-resilient subsets of persisters that do not actually exist.”
These findings could fundamentally change the direction of antibiotics research. Newer, real-time single-cell analysis techniques reveal the true behavior of bacteria under treatment, emphasizing the need to study bacterial behavior under physiologically relevant conditions.
“Our work underlines the importance of studying bacterial behavior and antibiotic effects live and under physiologically relevant conditions,” Bumann added.
This research is part of the National Center of Competence in Research (NCCR) “AntiResist,” a consortium focusing on innovative strategies to fight bacterial infections. The insights from this study are a significant step toward more effective therapies against stubborn infections, shifting focus from the previously misunderstood persisters to the broader issue of nutrient starvation.