
A new single-cell “bacteria surveillance” method reveals whether antibiotics truly kill infections—or just leave them waiting to strike back.
Antibiotics are usually evaluated by how well they stop bacteria from growing in laboratory tests. What matters just as much, though, is whether those drugs actually kill the bacteria inside the human body. Scientists at the University of Basel have now introduced a new way to measure how effectively antibiotics eliminate bacteria, rather than simply slowing them down.
This distinction is increasingly important as antibiotic resistance continues to rise. Resistant bacteria are one of the most serious global health challenges today. Genetic mutations allow many bacteria to withstand commonly used drugs, making infections harder and harder to treat.
When Bacteria Survive Without Resistance
Even bacteria that are not resistant can sometimes endure antibiotic treatment. This often happens when bacteria enter a dormant state. While dormant bacteria stop multiplying, antibiotics may fail to kill them. Once treatment ends, these bacteria can become active again and cause the infection to return.
This problem is especially serious for long-lasting infections such as tuberculosis and other complex bacterial diseases that require months of therapy. In these cases, doctors need antibiotics that fully eliminate the bacteria and leave no survivors behind.
Limits of Traditional Lab Tests
Most standard laboratory tests only show whether a drug prevents bacteria from growing. They do not reliably indicate whether the bacteria are dead. To address this gap, a research team led by Dr. Lucas Boeck from the Department of Biomedicine at the University of Basel and University Hospital Basel developed a new testing approach designed to better predict real treatment outcomes. Their work was published in the journal Nature Microbiology.
Filming the Fate of Individual Bacteria
The new approach, called “antimicrobial single-cell testing,” relies on high-resolution microscopy to observe millions of individual bacteria across thousands of test conditions. “We use it to film each individual bacterium over several days and observe whether and how quickly a drug actually kills it,” explains Lucas Boeck.
By tracking bacteria one cell at a time, the method shows exactly how many bacteria are eliminated and how efficiently a treatment works.
To validate the technique, the team tested 65 different drug combinations against Mycobacterium tuberculosis, the bacterium that causes tuberculosis. They also analyzed bacterial samples from 400 patients with another difficult lung infection caused by Mycobacterium abscessus, a close relative of the tuberculosis pathogen.
Why Some Bacteria Outlast Treatment
The researchers found major differences between drug combinations and also between bacterial strains taken from different patients. Specialists refer to this variation as antibiotic tolerance. Further analysis revealed that specific genetic traits help some bacteria endure treatment and effectively wait it out.
“The better bacteria tolerate an antibiotic, the lower the chances of therapeutic success are for the patients,” says Lucas Boeck. When compared with results from animal experiments and clinical studies, the new testing method closely matched how well different treatments cleared infections in real-world settings.
Benefits for Patients and Drug Development
So far, antimicrobial single-cell testing has mainly been used for research, but it may eventually be applied in hospitals and pharmaceutical development. According to Boeck, the technique could help doctors choose antibiotic therapies that are better matched to the specific bacterial strain infecting each patient.
“Our test method allows us to tailor antibiotic therapies specifically to the bacterial strains in individual patients,” he says. Improved insight into the genetics behind antibiotic tolerance could also lead to faster and simpler testing methods, as well as more accurate predictions of how effective new antibiotics will be during development.
“Last but not least, the data can help researchers to better understand the survival strategies of pathogens and thus lay the foundation for new, more effective therapeutic approaches,” Boeck adds.
Reference: “Large-scale testing of antimicrobial lethality at single-cell resolution predicts mycobacterial infection outcomes” by Alexander Jovanovic, Frederick K. Bright, Ahmad Sadeghi, Basil Wicki, Santiago E. Caño Muñiz, Greta C. Giannini, Sara Toprak, Loïc Sauteur, Anna Rodoni, Andreas Wüst, Andréanne Lupien, Sonia Borrell, Dorothy M. Grogono, Nicole E. Wheeler, Philippe Dehio, Johannes Nemeth, Hans Pargger, Rachel Thomson, Scott C. Bell, Sebastien Gagneux, Josephine M. Bryant, Tingying Peng, Andreas H. Diacon, R. Andres Floto, Michael Abanto and Lucas Boeck, 9 January 2026, Nature Microbiology.
DOI: 10.1038/s41564-025-02217-y
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