Projects per year
Abstract
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.
Original language | English |
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Article number | 729 |
Pages (from-to) | 1-16 |
Number of pages | 16 |
Journal | Antibiotics |
Volume | 9 |
Issue number | 11 |
Early online date | 23 Oct 2020 |
DOIs | |
Publication status | Published - 30 Nov 2020 |
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Dive into the research topics of 'The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C'. Together they form a unique fingerprint.Projects
- 1 Finished
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Understanding the Evolutionary Origins and Molecular Mechanisms of Antimicrobial Peptide Resistance
Gebhard, S. (PI)
Biotechnology and Biological Sciences Research Council
1/04/16 → 31/03/19
Project: Research council
Equipment
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Microplate reader BMG Labtech CLARIOstar
Material and Chemical Characterisation (MC2)Facility/equipment: Equipment