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Article

The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C

1
LOEWE Centre for Synthetic Microbiology, Philipps-Universität Marburg, Hans-Meerwein-Strasse 6, 35032 Marburg, Germany
2
School of Molecular Sciences, The University of Western Australia, Crawley 6009, WA, Australia
3
Biological Chemistry Group, Institute of Biology Leiden, Leiden University, Sylviusweg72, 2333 BE Leiden, The Netherlands
4
Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
5
Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
*
Author to whom correspondence should be addressed.
Antibiotics 2020, 9(11), 729; https://doi.org/10.3390/antibiotics9110729
Received: 29 September 2020 / Revised: 19 October 2020 / Accepted: 21 October 2020 / Published: 23 October 2020
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
Cell wall antibiotics are important tools in our fight against Gram-positive pathogens, but many strains become increasingly resistant against existing drugs. Laspartomycin C is a novel antibiotic that targets undecaprenyl phosphate (UP), a key intermediate in the lipid II cycle of cell wall biosynthesis. While laspartomycin C has been thoroughly examined biochemically, detailed knowledge about potential resistance mechanisms in bacteria is lacking. Here, we use reporter strains to monitor the activity of central resistance modules in the Bacillus subtilis cell envelope stress response network during laspartomycin C attack and determine the impact on the resistance of these modules using knock-out strains. In contrast to the closely related UP-binding antibiotic friulimicin B, which only activates ECF σ factor-controlled stress response modules, we find that laspartomycin C additionally triggers activation of stress response systems reacting to membrane perturbation and blockage of other lipid II cycle intermediates. Interestingly, none of the studied resistance genes conferred any kind of protection against laspartomycin C. While this appears promising for therapeutic use of laspartomycin C, it raises concerns that existing cell envelope stress response networks may already be poised for spontaneous development of resistance during prolonged or repeated exposure to this new antibiotic. View Full-Text
Keywords: laspartomycin C; friulimicin B; Bacillus subtilis; cell wall inhibition; stress response laspartomycin C; friulimicin B; Bacillus subtilis; cell wall inhibition; stress response
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MDPI and ACS Style

Diehl, A.; Wood, T.M.; Gebhard, S.; Martin, N.I.; Fritz, G. The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C. Antibiotics 2020, 9, 729. https://doi.org/10.3390/antibiotics9110729

AMA Style

Diehl A, Wood TM, Gebhard S, Martin NI, Fritz G. The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C. Antibiotics. 2020; 9(11):729. https://doi.org/10.3390/antibiotics9110729

Chicago/Turabian Style

Diehl, Angelika, Thomas M. Wood, Susanne Gebhard, Nathaniel I. Martin, and Georg Fritz. 2020. "The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C" Antibiotics 9, no. 11: 729. https://doi.org/10.3390/antibiotics9110729

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