dc.identifier.uri |
http://dx.doi.org/10.15488/3389 |
|
dc.identifier.uri |
http://www.repo.uni-hannover.de/handle/123456789/3419 |
|
dc.contributor.author |
Donner, Jannik
|
|
dc.contributor.author |
Reck, Michael
|
|
dc.contributor.author |
Bunk, Boyke
|
|
dc.contributor.author |
Jarek, Michael
|
|
dc.contributor.author |
App, Constantin Benjamin
|
|
dc.contributor.author |
Meier-Kolthoff, Jan P.
|
|
dc.contributor.author |
Overmann, Jörg
|
|
dc.contributor.author |
Müller, Rolf
|
|
dc.contributor.author |
Kirschning, Andreas
|
|
dc.contributor.author |
Wagner-Döbler, Irene
|
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dc.date.accessioned |
2018-05-23T11:04:01Z |
|
dc.date.available |
2018-05-23T11:04:01Z |
|
dc.date.issued |
2017 |
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dc.identifier.citation |
Donner, J.; Reck, M.; Bunk, B.; Jarek, M.; App, C.B. et al.: The biofilm inhibitor carolacton enters Gram-negative cells: Studies using a Tol-Cdeficient strain of Escherichia coli. In: mSphere 2 (2017), Nr. 5, e00375-17. DOI: https://doi.org/10.1128/mSphere.00375-17 |
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dc.description.abstract |
The myxobacterial secondary metabolite carolacton inhibits growth of Streptococcus pneumoniae and kills biofilm cells of the caries- and endocarditisassociated pathogen Streptococcus mutans at nanomolar concentrations. Here, we studied the response to carolacton of an Escherichia coli strain that lacked the outer membrane protein TolC. Whole-genome sequencing of the laboratory E. coli strain TolC revealed the integration of an insertion element, IS5, at the tolC locus and a close phylogenetic relationship to the ancient E. coli K-12. We demonstrated via transcriptome sequencing (RNA-seq) and determination of MIC values that carolacton penetrates the phospholipid bilayer of the Gram-negative cell envelope and inhibits growth of E. coli TolC at similar concentrations as for streptococci. This inhibition is completely lost for a C-9 (R) epimer of carolacton, a derivative with an inverted stereocenter at carbon atom 9 [(S) → (R)] as the sole difference from the native molecule, which is also inactive in S. pneumoniae and S. mutans, suggesting a specific interaction of native carolacton with a conserved cellular target present in bacterial phyla as distantly related as Firmicutes and Proteobacteria. The efflux pump inhibitor (EPI) phenylalanine arginine β-naphthylamide (PAβN), which specifically inhibits AcrAB-TolC, renders E. coli susceptible to carolacton. Our data indicate that carolacton has potential for use in antimicrobial chemotherapy against Gram-negative bacteria, as a single drug or in combination with EPIs. Strain E. coli TolC has been deposited at the DSMZ; together with the associated RNA-seq data and MIC values, it can be used as a reference during future screenings for novel bioactive compounds. © 2017 Donner et al. |
eng |
dc.language.iso |
eng |
|
dc.publisher |
Washington : American Society for Microbiology |
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dc.relation.ispartofseries |
mSphere 2 (2017), Nr. 5 |
|
dc.rights |
CC BY 4.0 Unported |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Antimicrobial activity |
eng |
dc.subject |
Antimicrobial agents |
eng |
dc.subject |
Carolacton |
eng |
dc.subject |
Drug efflux |
eng |
dc.subject |
Drug resistance mechanisms |
eng |
dc.subject |
Efflux pumps |
eng |
dc.subject |
Gene sequencing |
eng |
dc.subject |
Genome analysis |
eng |
dc.subject |
Gram-negative bacteria |
eng |
dc.subject.ddc |
570 | Biowissenschaften, Biologie
|
ger |
dc.title |
The biofilm inhibitor carolacton enters Gram-negative cells: Studies using a Tol-Cdeficient strain of Escherichia coli |
eng |
dc.type |
Article |
|
dc.type |
Text |
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dc.relation.issn |
2379-5042 |
|
dc.relation.doi |
https://doi.org/10.1128/mSphere.00375-17 |
|
dc.bibliographicCitation.issue |
5 |
|
dc.bibliographicCitation.volume |
2 |
|
dc.bibliographicCitation.firstPage |
e00375-17 |
|
dc.description.version |
publishedVersion |
|
tib.accessRights |
frei zug�nglich |
|