Evidence map›Paper›PMID 42663661›Full record

ArticleApplied microbiology and biotechnology2026

Construction of a novel reporter strain indicating inhibition of cell wall biosynthesis.

Maike Laura Karcher, Annette Siskowski, Chantal Müller, Laura Engel, Vincent Franz, Susanne H Kirsch, Birthe Sandargo, Tanja Schneider, Gabriele Bierbaum

Abstract read
In one paragraph

Article in Applied microbiology and biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Maike Laura KarcherInstitute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany. s74mkarc@uni-bonn.de.ORCID http://orcid.org/0009-0000-9804-8173
Annette SiskowskiInstitute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany.
Chantal MüllerInstitute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany.
Laura EngelInstitute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany.
Vincent FranzInstitute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany.
Susanne H KirschHelmholtz Centre for Infection Research (HZI), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), 66123, Saarbrücken, Germany.ORCID http://orcid.org/0000-0003-1294-0182
Birthe SandargoGerman Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124, Braunschweig, Germany.
Tanja SchneiderInstitute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, 53115, Bonn, Germany.
Gabriele BierbaumInstitute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany.ORCID http://orcid.org/0000-0002-2933-8473

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The WalRK two-component system monitors cell wall biosynthesis, and its activity decreases when biosynthesis is inhibited. As WalRK is essential for many Gram-positive bacteria, including Staphylococcus aureus and Bacillus subtilis, directly inhibiting WalK would disrupt cell wall biosynthesis and result in cell death. This study presents the construction of new reporter strains with two WalRK-dependent promoters: PiseA and PssaA. These reporter strains enable indirect in vivo measurement of WalRK activity based on luminescence. We evaluated these reporters in combination with the established PliaI reporter system, which is regulated by LiaRS, in order to improve the identification of cell wall inhibitors during the screening of natural products. The WalRK-dependent PiseA reporter yielded specific responses to almost all known cell wall biosynthesis inhibitors, including β-lactams, tunicamycin, glycopeptides, daptomycin, and fosfomycin, with no discernible response to other antibiotic classes. Furthermore, combining the PliaI reporter system with the PiseA reporter enhanced the range of potential cell wall inhibitors that could be detected. Deleting the gene of the eukaryotic-like Ser/Thr kinase PrkC increased the PiseA signal obtained with certain antibiotics, as well as after a longer incubation period. Additionally, deletion of prkC lowered PliaI expression in the presence of lipid II-targeting antibiotics. Screening natural products with an unknown mode of action identified several compounds that elicited vancomycin-like patterns with the reporter systems, indicating potential cell wall inhibitory activity. Overall, combining WalRK and LiaRS reporters enables a rapid, complementary evaluation of cell wall stress responses, providing a powerful method for discovering new cell wall-targeting antibiotics. KEY POINTS: • The PiseA/PssaA reporters enable continuous in vivo observation of WalRK activity • Cell envelope stress responses are differentially sensed by WalRK and LiaRS • The PiseA reporter strain detects nearly all cell wall biosynthesis inhibitors.

Indexed as

Anti-Bacterial AgentsBacillus subtilisBacterial ProteinsCell WallGenes, ReporterStaphylococcus aureusGene Expression Regulation, BacterialPromoter Regions, GeneticAnti-Bacterial AgentsBacterial ProteinsCell envelope stressCell wall biosynthesisLiaRS stress responseLuciferase reporter assayPrkC kinaseWalRK (YycFG) two-component system

Identifiers

PMID42663661
PMCPMC13525142

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.