Applicability of Chromatographic Co-Elution for Antibiotic Target Identification

Sina Schäkermann; Dominik Wüllner; Abdulkadir Yayci; Andrew Emili; Julia Elisabeth Bandow

doi:10.1002/pmic.202000038

Applicability of Chromatographic Co-Elution for Antibiotic Target Identification

Sina Schäkermann
, Dominik Wüllner
, Abdulkadir Yayci
, Andrew Emili
, Julia Elisabeth Bandow

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Identification of the molecular target is a crucial step in evaluating novel antibiotics. To support target identification, a label-free method based on chromatographic co-elution has previously been developed. Target identification by chromatographic coelution (TICC) exploits the alteration of the elution profile of target-bound drug versus free drug in ion exchange (IEX) chromatography to identify potential target proteins from elution fractions. The applicability of TICC for antibiotic research is investigated by evaluating which proteins, that is, putative targets, can be monitored in Bacillus subtilis. Coelution of components of known protein complexes provides a read-out for how well the native state of proteins is conserved during chromatography. Rifampicin, which targets RNA polymerase, is used in a proof-of-concept study.

Original language	English (US)
Article number	2000038
Journal	Proteomics
Volume	21
Issue number	1
DOIs	https://doi.org/10.1002/pmic.202000038
State	Published - Jan 1 2021
Externally published	Yes

Funding

S.S. and D.W. contributed equally to this work. The authors kindly acknowledge support with protein localization prediction by Dörte Becher. SSch is thankful for the kind introduction to TICC by members of the Emili lab, especially by Hui Peng and Hongbo Guo, and acknowledges a travel grant from the “Ruth‐und‐Gerd‐Massenberg” Foundation for an internship in the Emili lab. This work was supported by grants from the German Federal State of North Rhine‐Westphalia (NRW) (“Translation Innovativer Antibiotika“ and “Forschungsgroßgeräte der Länder“) as well as the German Federal State of North Rhine‐Westphalia and the European Union, European Regional Development Fund, Investing in your future (Research Infrastructure “Center for System‐based Antibiotic Research (CESAR)”) to JEB. S.S. and D.W. contributed equally to this work. The authors kindly acknowledge support with protein localization prediction by D?rte Becher. SSch is thankful for the kind introduction to TICC by members of the Emili lab, especially by Hui Peng and Hongbo Guo, and acknowledges a travel grant from the ?Ruth-und-Gerd-Massenberg? Foundation for an internship in the Emili lab. This work was supported by grants from the German Federal State of North Rhine-Westphalia (NRW) (?Translation Innovativer Antibiotika? and ?Forschungsgro?ger?te der L?nder?) as well as the German Federal State of North Rhine-Westphalia and the European Union, European Regional Development Fund, Investing in your future (Research Infrastructure ?Center for System-based Antibiotic Research (CESAR)?) to JEB. Open access funding enabled and organized by Projekt DEAL.

Funders
Cesar Timo-Iaria Laboratory
Center for System-based Antibiotic Research
German Federal State of North Rhine-Westphalia
German Federal State of North Rhine‐Westphalia
Natural Resources Wales
European Commission
European Regional Development Fund/European Social Fund FIS

Keywords

Bacillus subtilis
mode of action
protein complexes
protein–protein interaction
rifampicin

ASJC Scopus subject areas

Biochemistry
Molecular Biology

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10.1002/pmic.202000038

Cite this

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title = "Applicability of Chromatographic Co-Elution for Antibiotic Target Identification",

abstract = "Identification of the molecular target is a crucial step in evaluating novel antibiotics. To support target identification, a label-free method based on chromatographic co-elution has previously been developed. Target identification by chromatographic coelution (TICC) exploits the alteration of the elution profile of target-bound drug versus free drug in ion exchange (IEX) chromatography to identify potential target proteins from elution fractions. The applicability of TICC for antibiotic research is investigated by evaluating which proteins, that is, putative targets, can be monitored in Bacillus subtilis. Coelution of components of known protein complexes provides a read-out for how well the native state of proteins is conserved during chromatography. Rifampicin, which targets RNA polymerase, is used in a proof-of-concept study.",

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Applicability of Chromatographic Co-Elution for Antibiotic Target Identification

Abstract

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Keywords

ASJC Scopus subject areas

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