Scientists at the University of Basel have developed a novel testing method to determine whether antibiotics actually eliminate bacteria or merely halt their growth. This approach, called antimicrobial single-cell testing, tracks individual bacteria under a microscope to assess drug effectiveness more accurately. The findings, published in Nature Microbiology, highlight variations in bacterial tolerance to treatments for tuberculosis and other lung infections.
Antibiotic resistance poses a major global health challenge, with bacteria increasingly evading common drugs through genetic mutations. Even non-resistant bacteria can persist by entering a dormant state, where they cease multiplying but survive treatment, potentially reactivating infections later. This issue is particularly acute in prolonged therapies for tuberculosis and related lung conditions caused by Mycobacterium tuberculosis and Mycobacterium abscessus.
To address limitations in traditional lab tests, which focus on growth inhibition rather than outright killing, researchers led by Dr. Lucas Boeck from the University of Basel's Department of Biomedicine and University Hospital Basel introduced antimicrobial single-cell testing. This technique employs advanced microscopy to monitor millions of individual bacteria over several days under thousands of conditions. "We use it to film each individual bacterium over several days and observe whether and how quickly a drug actually kills it," Boeck explained.
In demonstrations, the team evaluated 65 drug combinations against Mycobacterium tuberculosis and analyzed samples from 400 patients with Mycobacterium abscessus infections. Results showed significant differences in efficacy between drug mixes and across bacterial strains, influenced by genetic factors that promote antibiotic tolerance. "The better bacteria tolerate an antibiotic, the lower the chances of therapeutic success are for the patients," Boeck noted. The method's predictions aligned closely with outcomes from clinical studies and animal models.
Currently used in research, this testing could extend to clinical settings and pharmaceutical development. It enables personalized antibiotic selection based on specific bacterial strains. "Our test method allows us to tailor antibiotic therapies specifically to the bacterial strains in individual patients," Boeck said. Furthermore, insights into bacterial survival mechanisms may inspire novel treatments. "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," he added.
The study underscores the need for precise tools in combating persistent infections, potentially improving patient outcomes and drug innovation.
