Bumann Lab: Why antibiotics can fail even against non-resistant bacteria
Antibiotics are indispensable in the treatment of bacterial infections. But why are they sometimes ineffective, even when the bacteria are not resistant? Researchers led by Prof. Dirk Bumann at the Biozentrum, University of Basel, challenge the conventional understanding of particularly resilient bacteria and highlight the limitations of traditional laboratory methods. The study has recently been published in “Nature”.
In certain infectious diseases, antibiotics are less effective than expected, as seen in infections caused by Salmonella bacteria, which can lead to illnesses like typhoid fever. For many years, researchers believed that a small subset of dormant bacteria are the main problem in fighting infections. These so-called persisters can survive antibiotic treatment and cause relapses later. Researchers worldwide have been working on new therapies aimed at targeting and eliminating these “sleeping” bacteria.
In a new study, Prof. Dirk Bumann’s team from the Biozentrum of the University of Basel challenges the prevailing concept of persisters. “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,” explains Bumann. “We have been able to demonstrate that standard laboratory tests of antimicrobial clearance produce misleading results, giving a false impression of persisters.”
Nutrient starvation increases Salmonella resilience
The researchers investigated antimicrobial clearance in both Salmonella-infected mice and tissue-mimicking laboratory models. The body’s defense mechanisms against bacteria often include reducing the availability of nutrients. The researchers have now revealed that nutrient starvation is the main reason for antibiotic failures.
“Under nutrient-scarce conditions, bacteria grow very slowly,” says Bumann. “This may seem good at first, but is actually a problem because most antibiotics only gradually kill slowly growing bacteria.” As a result, the drugs are much less effective, and relapses can occur even after prolonged therapy.
Real-time analyses reveal misconception
The scientists used an innovative method to monitor antibiotic action in single bacteria in real time. “We demonstrated that nearly the entire Salmonella population survives antibiotic treatment for extended periods, not just a small subset of hyper-resilient persisters,” says Joseph Fanous, the study’s first author.
Limitations of traditional methods
A major issue with the standard methods used worldwide for decades is that they measure bacterial survival only indirectly and with delays, thus leading to distorted results. “Traditional tests underestimate the number of surviving bacteria,” explains Fanous. “And they falsely suggest the presence of hyper-resilient subsets of persisters that do not actually exist.” This misinterpretation has influenced research for many years.
Novel tools for antibiotics research
These findings could fundamentally change antibiotics research. “Our work underlines the importance of studying bacterial behavior and antibiotic effects live and under physiologically relevant conditions,” emphasizes Bumann. “In a few years, modern methods like real-time single-cell analysis will hopefully become standard.” Shifting the focus from persisters to the impact of nutrient starvation is an important step toward more effective therapies against difficult-to-treat infections.
The project is part of the National Center of Competence in Research (NCCR) “AntiResist”. The research consortium aims to develop innovative strategies to combat bacterial infections. Prof. Dirk Bumann is one of the directors of the NCCR “AntiResist”.
Original publication:
Joseph Fanous, Beatrice Claudi, Vishwachi Tripathi, Jiagui Li, Frédéric Goormaghtigh, Dirk Bumann. Limited impact of Salmonella stress and persisters on antibiotic clearance. Nature; published online
Caption:
EN: Scanning-electron microscopy image showing Salmonella bacteria. (Nano Imaging Lab SNI/Biozentrum University of Basel)
DE: Rasterelektronenmikroskopische Aufnahme von Salmonella-Bakterien. (Nano Imaging Lab SNI/Biozentrum University of Basel)
