Large-scale testing of antimicrobial lethality at single-cell resolution predicts mycobacterial infection outcomes

In vitro antibiotic testing is important for guiding therapy and drug development. Current methods are focused on growth inhibition in bulk bacterial populations but often fail to accurately predict treatment responses. Here we introduce Antimicrobial Single-Cell Testing (ASCT), a large-scale live-cell imaging approach that quantifies bacterial killing in real time at single-cell resolution. By tracking over 140 million mycobacteria and analysing ~20,000 time-kill curves, we identify key determinants of antibiotic killing and its clinical relevance. For Mycobacterium tuberculosis, we found that drug-specific killing dynamics in starved bacteria, rather than growth inhibition or killing of growing cells,…

• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Awards: 185792, 180541, 177799, 215557