Implementing best practices on data generation and reporting of Mycobacterium tuberculosis in vitro assays within the ERA4TB consortium
Rob C. van Wijk,
Ainhoa Lucía,
Pavan Kumar Sudhakar,
Lindsay Sonnenkalb,
Cyril Gaudin,
Eik Hoffmann,
Bérénice Dremierre,
Diana Angélica Aguilar-Ayala,
Michael Dal Molin,
Jan Rybniker,
Stefano de Giorgi,
Laura Cioetto-Mazzabò,
Greta Segafreddo,
Riccardo Manganelli,
Giulia Degiacomi,
Deborah Recchia,
Maria Rosalia Pasca,
Ulrika S.H. Simonsson,
Santiago Ramón-García
Affiliations
Rob C. van Wijk
Department of Pharmaceutical Biosciences, Uppsala University, 75124 Uppsala, Sweden
Ainhoa Lucía
Department of Microbiology, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
Pavan Kumar Sudhakar
Data collaboration center, Critical Path Institute Ltd, D11 YNR2 Dublin, Ireland
Lindsay Sonnenkalb
Molecular and Experimental Mycobacteriology, Research Center Borstel Leibniz Lung Center, 23845 Borstel, Germany
Cyril Gaudin
Center for Infection and Immunity of Lille, Institut Pasteur de Lille, 59019 Lille, France
Eik Hoffmann
Center for Infection and Immunity of Lille, Institut Pasteur de Lille, 59019 Lille, France
Bérénice Dremierre
Center for Infection and Immunity of Lille, Institut Pasteur de Lille, 59019 Lille, France
Diana Angélica Aguilar-Ayala
Department of Microbiology, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
Michael Dal Molin
Department I of Internal Medicine, Division of Infectious Diseases, University of Cologne, 50937 Cologne, Germany; Faculty of Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany
Jan Rybniker
Department I of Internal Medicine, Division of Infectious Diseases, University of Cologne, 50937 Cologne, Germany; Faculty of Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany
Stefano de Giorgi
Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
Laura Cioetto-Mazzabò
Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
Greta Segafreddo
Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
Riccardo Manganelli
Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
Giulia Degiacomi
Department of Biology and Biotechnology Lazzaro Spallanzani, University of Pavia, 27100 Pavia, Italy
Deborah Recchia
Department of Biology and Biotechnology Lazzaro Spallanzani, University of Pavia, 27100 Pavia, Italy
Maria Rosalia Pasca
Department of Biology and Biotechnology Lazzaro Spallanzani, University of Pavia, 27100 Pavia, Italy
Ulrika S.H. Simonsson
Department of Pharmaceutical Biosciences, Uppsala University, 75124 Uppsala, Sweden
Santiago Ramón-García
Department of Microbiology, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain; CIBER Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain; Research & Development Agency of Aragon Foundation (Fundación ARAID), 50009 Zaragoza, Spain; Corresponding author
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 the 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 program.
