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Jovanovic, A.* ; Bright, F.K.* ; Sadeghi, A.* ; Wicki, B.* ; Caño Muñiz, S.E.* ; Giannini, G.C.* ; Toprak, S.* ; Sauteur, L.* ; Rodoni, A.* ; Wüst, A.* ; Lupien, A.* ; Borrell, S.* ; Grogono, D.M.* ; Wheeler, N.E.* ; Dehio, P.* ; Nemeth, J.* ; Pargger, H.* ; Thomson, R.* ; Bell, S.C.* ; Gagneux, S.* ; Bryant, J.M.* ; Peng, T. ; Diacon, A.H.* ; Floto, R.A.* ; Abanto, M.* ; Boeck, L.*

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

Nat. Microbiol. 11, 566–583 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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, predict regimen efficacy in mice and humans. Extending this approach to Mycobacterium abscessus and comparing 405 bacterial strains, we show that antibiotic killing is also a genetically encoded bacterial trait (drug tolerance). We demonstrate that tolerance patterns cluster by antibiotic targets, identify a phage protein that modulates antibiotic killing, and show that strain-specific killing dynamics are associated with individual patient outcomes independent of drug resistance. Together, these findings establish a framework that reveals how drug properties and bacterial diversity shape treatment responses, offering a path to more effective and personalized therapies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Antibiotics ; Lethality ; Antimicrobial ; Bacteria ; Drug ; Personalized Medicine ; Antibiotic Resistance ; Drug Development ; Multidrug Tolerance; Antibiotic Tolerance; Genome; Association; Impact; Persistence; Mutations; Emergence; Mortality; Framework; Alignment
ISSN (print) / ISBN 2058-5276
e-ISSN 2058-5276
Zeitschrift Nature microbiology
Quellenangaben Band: 11, Heft: , Seiten: 566–583 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Artifical Intelligence Cooperation Unit (HAICU)
Förderungen Schweizerischer Nationalfonds zur Frderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
Bangerter Rhyner Foundation, Goldschmidt Jacobson Foundation, Helmut Horten Foundation, Swiss Society for Pneumology, Clotta Foundation