Mycobacterium tuberculosis time kill assay data of the standardized protocol within the ERA4TB consortium

Data corresponding to the manuscript:

  

Implementing best practises on data generation and reporting of Mycobacterium tuberculosis in vitro assays within the ERA4TB consortium

Rob C van Wijk 1,a, Ainhoa Lucia 2,a, Pavan Kumar Sudhakar3, Lindsay Sonnenkalb 4, Cyril Gaudin 5, Eik Hoffmann 5, Diana Angélica Aguilar-Ayala 2, Michael Dal Molin 6,7, Jan Rybniker 6,7,8, Stefano de Giorgi 9, Laura Cioetto-Mazzabò 9, Greta Segafreddo 9, Riccardo Manganelli 9, Giulia Degiacomi 10, Deborah Recchia 10, Maria Rosalia Pasca 10, Ulrika S H Simonson 1, Santiago Ramón-García 2,11,12,*   on behalf of the ERA4TB consortium

Summary

Tuberculosis (TB) is the historical leading cause of death by a single infectious agent. The European Regimen Accelerator for Tuberculosis (ERA4TB) is a public-private partnership of 30+ institutions with the objective to progress new anti-TB regimens into the clinic. Thus, robust and replicable results across independent laboratories are essential for reliable interpretation of treatment efficacy. A standardization workgroup unified in vitro protocols and data reporting templates. Time-kill assays provide essential input data for pharmacometric model informed translation of single agents and regimens activity from in vitro to in vivo and clinic. Five conditions were assessed by time-kill assays in six independent laboratories using four bacterial plating methods. Baseline bacterial burden varied between laboratories but variability was limited in net drug effect, confirming 2.5 µL equally robust as 100 µL plating. This exercise establishes the foundations of collaborative data generation, reporting and integration within the overarching Antimicrobial Resistance Accelerator programme. 

a authors contributed equally, * corresponding author: santiramon@unizar.es 

  

1. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden

2. Department of Microbiology, University of Zaragoza, Zaragoza, Spain

3. Data collaboration center, Critical Path Institute Ltd, Dublin, Ireland

4. Molecular and Experimental Mycobacteriology, Research Center Borstel Leibniz Lung Center, Germany

5. Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France

6. Department I of Internal Medicine, Division of Infectious Diseases, University of Cologne, Cologne, Germany

7. Faculty of Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

8. German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany

9. Department of Molecular Medicine, University of Padova, Padova, Italy

10. Laboratory of Molecular Microbiology, Department of Biology and Biotechnology Lazzaro Spallanzani, University of Pavia, Pavia, Italy

11. CIBER Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

12. Research & Development Agency of Aragon Foundation (Fundación ARAID), Zaragoza, Spain

Data description

Bacterial burden over time data for the time kill assay performed in six laboratories, as described in the STAR Methods and presented in the Results of Van Wijk et al (10.1016/j.isci.2023.106411). Data is grouped by treatment (0: untreated, 1: 1x MIC moxifloxacin, 2: 10x MIC moxifloxacin, 3: 1x MIC isoniazid, 4: 10x MIC isoniazid), and plating condition (0: 100uL quad, 1: 10uL 4 drops 2: 10uL single drop 3: 2.5uL single drop). Time in days, volume in μL, bacterial burden in (log10) CFU/mL. AQL = above quantification limit, BQL = below quantification limit.