Anatomy of the bacitracin resistance network in Bacillus subtilis

Jara Radeck, Susanne Gebhard, Peter Shevlin Orchard, Marion Kirchner, Stephanie Bauer, Thorsten Mascher, Georg Fritz

Research output: Contribution to journalArticle

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Abstract

Protection against antimicrobial peptides (AMPs) often involves the parallel production of multiple, well-characterized resistance determinants. So far, little is known about how these resistance modules interact and how they jointly protect the cell. Here, we studied the interdependence between different layers of the envelope stress response of Bacillus subtilis when challenged with the lipid II cycle-inhibiting AMP bacitracin. The underlying regulatory network orchestrates the production of the ABC transporter BceAB, the UPP phosphatase BcrCand the phage-shock proteins LiaIH. Our systems-level analysis reveals a clear hierarchy,allowing us to discriminate between primary (BceAB) and secondary (BcrC and LiaIH) layers ofbacitracin resistance. Deleting the primary layer provokes an enhanced induction of the secondary layer to partially compensate for this loss. This study reveals a direct role of LiaI H inbacitracin resistance, provides novel insights into the feedback regulation of the Lia system, anddemonstrates a pivotal role of BcrC in maintaining cell wall homeostasis. The compensatory regulation within the bacitracin network can also explain how gene expression noise propagates between resistance layers. We suggest that this active redundancy in the bacitracin resistance network of B. subtilis is a general principle to be found in many bacterial antibiotic resistance networks.
Original languageEnglish
Pages (from-to)607-620
JournalMolecular Microbiology
Volume100
Issue number4
Early online date27 Jan 2016
DOIs
Publication statusPublished - 10 Mar 2016

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Bacitracin
Bacillus subtilis
Anatomy
Bacterial Drug Resistance
Peptides
ATP-Binding Cassette Transporters
Phosphoric Monoester Hydrolases
Bacteriophages
Cell Wall
Noise
Shock
Homeostasis
Gene Expression
Proteins

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Radeck, J., Gebhard, S., Orchard, P. S., Kirchner, M., Bauer, S., Mascher, T., & Fritz, G. (2016). Anatomy of the bacitracin resistance network in Bacillus subtilis. Molecular Microbiology, 100(4), 607-620. https://doi.org/10.1111/mmi.13336

Anatomy of the bacitracin resistance network in Bacillus subtilis. / Radeck, Jara; Gebhard, Susanne; Orchard, Peter Shevlin; Kirchner, Marion; Bauer, Stephanie; Mascher, Thorsten; Fritz, Georg.

In: Molecular Microbiology, Vol. 100, No. 4, 10.03.2016, p. 607-620.

Research output: Contribution to journalArticle

Radeck, J, Gebhard, S, Orchard, PS, Kirchner, M, Bauer, S, Mascher, T & Fritz, G 2016, 'Anatomy of the bacitracin resistance network in Bacillus subtilis', Molecular Microbiology, vol. 100, no. 4, pp. 607-620. https://doi.org/10.1111/mmi.13336
Radeck J, Gebhard S, Orchard PS, Kirchner M, Bauer S, Mascher T et al. Anatomy of the bacitracin resistance network in Bacillus subtilis. Molecular Microbiology. 2016 Mar 10;100(4):607-620. https://doi.org/10.1111/mmi.13336
Radeck, Jara ; Gebhard, Susanne ; Orchard, Peter Shevlin ; Kirchner, Marion ; Bauer, Stephanie ; Mascher, Thorsten ; Fritz, Georg. / Anatomy of the bacitracin resistance network in Bacillus subtilis. In: Molecular Microbiology. 2016 ; Vol. 100, No. 4. pp. 607-620.
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