Anatomy of the bacitracin resistance network in Bacillus subtilis.

Molecular Microbiology
Jara RadeckGeorg Fritz

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 BcrC and 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 of bacitracin 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 LiaIH in bacitracin resistance, provides novel insights into the feedback regulation of the Lia system, and demonstrates 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 th...Continue Reading

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Citations

Dec 25, 2019·Antimicrobial Agents and Chemotherapy·Carolin M KobrasSusanne Gebhard
May 5, 2020·Journal of Basic Microbiology·Ali HassanTafail A Mughal
Jul 25, 2019·Antimicrobial Agents and Chemotherapy·Amy G PraterYousif Shamoo
Jun 23, 2019·Nature Communications·Hannah PiepenbreierGeorg Fritz
May 4, 2017·Journal of Bacteriology·Reed M Stubbendieck, Paul D Straight
Jan 8, 2020·Sensors·Zhiyong SunAinhoa Revilla-Guarinos
Aug 9, 2020·NPJ Biofilms and Microbiomes·Jhonatan A Hernandez-ValdesOscar P Kuipers
Oct 30, 2020·Antibiotics·Angelika DiehlGeorg Fritz
Mar 27, 2021·Angewandte Chemie·Daniel A WirtzTanja Schneider
May 29, 2021·Frontiers in Molecular Biosciences·Jessica R Willdigg, John D Helmann
Aug 15, 2021·Nucleic Acids Research·Wenliang HaoZhemin Zhou
Apr 27, 2019·ACS Chemical Biology·Stephanie TanJustin R Nodwell

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