Comparison of Proteomic Responses as Global Approach to Antibiotic Mechanism of Action Elucidation

Author:

Senges Christoph H. R.1,Stepanek Jennifer J.1,Wenzel Michaela1,Raatschen Nadja1,Ay Ümran1,Märtens Yvonne1,Prochnow Pascal1,Vázquez Hernández Melissa1,Yayci Abdulkadir1,Schubert Britta1,Janzing Niklas B. M.1,Warmuth Helen L.1,Kozik Martin1,Bongard Jens1,Alumasa John N.2,Albada Bauke3,Penkova Maya3,Lukežič Tadeja4,Sorto Nohemy A.5,Lorenz Nicole3,Miller Reece G.3,Zhu Bingyao6,Benda Martin6,Stülke Jörg6,Schäkermann Sina1,Leichert Lars I.7,Scheinpflug Kathi8,Brötz-Oesterhelt Heike9,Hertweck Christian10,Shaw Jared T.5,Petković Hrvoje11,Brunel Jean M.12,Keiler Kenneth C.2ORCID,Metzler-Nolte Nils3,Bandow Julia E.1ORCID

Affiliation:

1. Applied Microbiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany

2. Biochemistry and Molecular Biology, Pennsylvania State University, State College, Pennsylvania, USA

3. Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr University Bochum, Bochum, Germany

4. Acies Bio, Ljubljana, Slovenia

5. Department of Chemistry, University of California—Davis, Davis, California, USA

6. Department of General Microbiology, Institute of Microbiology and Genetics, Georg-August University Göttingen, Göttingen, Germany

7. Microbial Biochemistry, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany

8. Peptide Lipid Interactions, Leibniz Institute for Molecular Pharmacology, Berlin, Germany

9. Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen, Tübingen, Germany

10. Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany

11. Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia

12. UMR MD1, Membranes et Cibles Thérapeutiques, Faculté de Pharmacie U1261 INSERM, Aix-Marseille Université, Marseille, France

Abstract

New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of Bacillus subtilis covering 91 antibiotics and comparator compounds, and a mathematical approach was developed to aid data analysis.

Funder

SPIRIT Slovenija

German Federal State of North Rhine-Westphalia

HHS | National Institutes of Health

Deutsche Forschungsgemeinschaft

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Ministrstvo za visoko šolstvo, znanost in tehnologijo

EC | European Regional Development Fund

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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