The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Angelika Diehl
- Thomas M Wood
- Susanne Gebhard
- Nathaniel I Martin
- Georg Fritz
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000592935100001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/antibiotics9110729
- Externe Identifier
- Clarivate Analytics Document Solution ID: OW5OG
- PubMed Identifier: 33114184
- ISSN
- 2079-6382
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- ANTIBIOTICS-BASEL
- Schlüsselwörter
- laspartomycin C
- friulimicin B
- Bacillus subtilis
- cell wall inhibition
- stress response
- Artikelnummer
- ARTN 729
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- The Cell Envelope Stress Response of <i>Bacillus subtilis</i> towards Laspartomycin C
- Sub types
- Article
- Ausgabe der Zeitschrift
- 9
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>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.</jats:p>
- Autoren
- Angelika Diehl
- Thomas M Wood
- Susanne Gebhard
- Nathaniel I Martin
- Georg Fritz
- DOI
- 10.3390/antibiotics9110729
- eISSN
- 2079-6382
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Antibiotics
- Sprache
- en
- Online publication date
- 2020
- Paginierung
- 729 - 729
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/antibiotics9110729
- Datum der Datenerfassung
- 2020
- Titel
- The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C
- Ausgabe der Zeitschrift
- 9
Data source: Crossref
- 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 <i>Bacillus subtilis</i> 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.
- Addresses
- LOEWE Centre for Synthetic Microbiology, Philipps-Universität Marburg, Hans-Meerwein-Strasse 6, 35032 Marburg, Germany.
- Autoren
- Angelika Diehl
- Thomas M Wood
- Susanne Gebhard
- Nathaniel I Martin
- Georg Fritz
- DOI
- 10.3390/antibiotics9110729
- eISSN
- 2079-6382
- Externe Identifier
- PubMed Identifier: 33114184
- PubMed Central ID: PMC7690785
- Funding acknowledgements
- European Research Council: ERC consolidator grant, grant agreement no. 725523
- Biotechnology and Biological Sciences Research Council: BB/M029255/1
- Deutsche Forschungsgemeinschaft: FR3673/1-2
- European Research Council: 725523
- Open access
- true
- ISSN
- 2079-6382
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Antibiotics (Basel, Switzerland)
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2020
- Open access status
- Open Access
- Paginierung
- E729
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2020
- Titel
- The Cell Envelope Stress Response of <i>Bacillus subtilis</i> towards Laspartomycin C.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 9
Files
https://www.mdpi.com/2079-6382/9/11/729/pdf?version=1603458638 https://europepmc.org/articles/PMC7690785?pdf=render
Data source: Europe PubMed Central
- 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.
- Date of acceptance
- 2020
- Autoren
- Angelika Diehl
- Thomas M Wood
- Susanne Gebhard
- Nathaniel I Martin
- Georg Fritz
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/33114184
- DOI
- 10.3390/antibiotics9110729
- Externe Identifier
- PubMed Central ID: PMC7690785
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: FR3673/1-2
- Biotechnology and Biological Sciences Research Council: BB/M029255/1
- European Research Council: ERC consolidator grant, grant agreement no. 725523
- ISSN
- 2079-6382
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Antibiotics (Basel)
- Schlüsselwörter
- Bacillus subtilis
- cell wall inhibition
- friulimicin B
- laspartomycin C
- stress response
- Sprache
- eng
- Country
- Switzerland
- PII
- antibiotics9110729
- Datum der Veröffentlichung
- 2020
- Status
- Published online
- Titel
- The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 9
Data source: PubMed
- Beziehungen:
- Property of