BceAB-Type Antibiotic Resistance Transporters Appear To Act by Target Protection of Cell Wall Synthesis
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Carolin M Kobras
- Hannah Piepenbreier
- Jennifer Emenegger
- Andre Sim
- Georg Fritz
- Susanne Gebhard
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000516763200071&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1128/AAC.02241-19
- eISSN
- 1098-6596
- Externe Identifier
- Clarivate Analytics Document Solution ID: KQ2MQ
- PubMed Identifier: 31871088
- ISSN
- 0066-4804
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
- Schlüsselwörter
- ABC transport
- antimicrobial peptide
- lipid II cycle
- Bacillus subtilis
- Artikelnummer
- ARTN e02241-19
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- BceAB-Type Antibiotic Resistance Transporters Appear To Act by Target Protection of Cell Wall Synthesis
- Sub types
- Article
- Ausgabe der Zeitschrift
- 64
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>Resistance against cell wall-active antimicrobial peptides in bacteria is often mediated by transporters. In low-GC-content Gram-positive bacteria, a common type of such transporters is BceAB-like systems, which frequently provide high-level resistance against peptide antibiotics that target intermediates of the lipid II cycle of cell wall synthesis. How a transporter can offer protection from drugs that are active on the cell surface, however, has presented researchers with a conundrum.</jats:p>
- Autoren
- Carolin M Kobras
- Hannah Piepenbreier
- Jennifer Emenegger
- Andre Sim
- Georg Fritz
- Susanne Gebhard
- DOI
- 10.1128/aac.02241-19
- eISSN
- 1098-6596
- ISSN
- 0066-4804
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Antimicrobial Agents and Chemotherapy
- Sprache
- en
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Herausgeber
- American Society for Microbiology
- Herausgeber URL
- http://dx.doi.org/10.1128/aac.02241-19
- Datum der Datenerfassung
- 2022
- Titel
- BceAB-Type Antibiotic Resistance Transporters Appear To Act by Target Protection of Cell Wall Synthesis
- Ausgabe der Zeitschrift
- 64
Data source: Crossref
- Abstract
- Resistance against cell wall-active antimicrobial peptides in bacteria is often mediated by transporters. In low-GC-content Gram-positive bacteria, a common type of such transporters is BceAB-like systems, which frequently provide high-level resistance against peptide antibiotics that target intermediates of the lipid II cycle of cell wall synthesis. How a transporter can offer protection from drugs that are active on the cell surface, however, has presented researchers with a conundrum. Multiple theories have been discussed, ranging from removal of the peptides from the membrane and internalization of the drug for degradation to removal of the cellular target rather than the drug itself. To resolve this much-debated question, we here investigated the mode of action of the transporter BceAB of <i>Bacillus subtilis</i> We show that it does not inactivate or import its substrate antibiotic bacitracin. Moreover, we present evidence that the critical factor driving transport activity is not the drug itself but instead the concentration of drug-target complexes in the cell. Our results, together with previously reported findings, lead us to propose that BceAB-type transporters act by transiently freeing lipid II cycle intermediates from the inhibitory grip of antimicrobial peptides and thus provide resistance through target protection of cell wall synthesis. Target protection has so far only been reported for resistance against antibiotics with intracellular targets, such as the ribosome. However, this mechanism offers a plausible explanation for the use of transporters as resistance determinants against cell wall-active antibiotics in Gram-positive bacteria where cell wall synthesis lacks the additional protection of an outer membrane.
- Addresses
- Department of Biology & Biochemistry, Milner Centre for Evolution, University of Bath, Bath, United Kingdom.
- Autoren
- Carolin M Kobras
- Hannah Piepenbreier
- Jennifer Emenegger
- Andre Sim
- Georg Fritz
- Susanne Gebhard
- DOI
- 10.1128/aac.02241-19
- eISSN
- 1098-6596
- Externe Identifier
- PubMed Identifier: 31871088
- PubMed Central ID: PMC7038271
- Funding acknowledgements
- Biotechnology and Biological Sciences Research Council: BB/M029255/1
- Deutsche Forschungsgemeinschaft: FR3673/1–2
- UK Research and Innovation | Biotechnology and Biological Sciences Research Council: BB/M029255/1
- Open access
- true
- ISSN
- 0066-4804
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Antimicrobial agents and chemotherapy
- Schlüsselwörter
- Cell Wall
- Bacillus subtilis
- Bacterial Proteins
- Drug Resistance, Bacterial
- Gene Expression Regulation, Bacterial
- Sprache
- eng
- Medium
- Electronic-Print
- Online publication date
- 2020
- Open access status
- Open Access
- Paginierung
- e02241 - e02219
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2019
- Titel
- BceAB-Type Antibiotic Resistance Transporters Appear To Act by Target Protection of Cell Wall Synthesis.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 64
Files
https://europepmc.org/articles/PMC7038271?pdf=render
Data source: Europe PubMed Central
- Abstract
- Resistance against cell wall-active antimicrobial peptides in bacteria is often mediated by transporters. In low-GC-content Gram-positive bacteria, a common type of such transporters is BceAB-like systems, which frequently provide high-level resistance against peptide antibiotics that target intermediates of the lipid II cycle of cell wall synthesis. How a transporter can offer protection from drugs that are active on the cell surface, however, has presented researchers with a conundrum. Multiple theories have been discussed, ranging from removal of the peptides from the membrane and internalization of the drug for degradation to removal of the cellular target rather than the drug itself. To resolve this much-debated question, we here investigated the mode of action of the transporter BceAB of Bacillus subtilis We show that it does not inactivate or import its substrate antibiotic bacitracin. Moreover, we present evidence that the critical factor driving transport activity is not the drug itself but instead the concentration of drug-target complexes in the cell. Our results, together with previously reported findings, lead us to propose that BceAB-type transporters act by transiently freeing lipid II cycle intermediates from the inhibitory grip of antimicrobial peptides and thus provide resistance through target protection of cell wall synthesis. Target protection has so far only been reported for resistance against antibiotics with intracellular targets, such as the ribosome. However, this mechanism offers a plausible explanation for the use of transporters as resistance determinants against cell wall-active antibiotics in Gram-positive bacteria where cell wall synthesis lacks the additional protection of an outer membrane.
- Date of acceptance
- 2019
- Autoren
- Carolin M Kobras
- Hannah Piepenbreier
- Jennifer Emenegger
- Andre Sim
- Georg Fritz
- Susanne Gebhard
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/31871088
- DOI
- 10.1128/AAC.02241-19
- eISSN
- 1098-6596
- Externe Identifier
- PubMed Central ID: PMC7038271
- Funding acknowledgements
- Biotechnology and Biological Sciences Research Council: BB/M029255/1
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Antimicrob Agents Chemother
- Schlüsselwörter
- ABC transport
- Bacillus subtilis
- antimicrobial peptide
- lipid II cycle
- Bacillus subtilis
- Bacterial Proteins
- Cell Wall
- Drug Resistance, Bacterial
- Gene Expression Regulation, Bacterial
- Sprache
- eng
- Country
- United States
- PII
- AAC.02241-19
- Datum der Veröffentlichung
- 2020
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2020
- Titel
- BceAB-Type Antibiotic Resistance Transporters Appear To Act by Target Protection of Cell Wall Synthesis.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 64
Data source: PubMed
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