The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target.

2.50
Hdl Handle:
http://hdl.handle.net/10033/617011
Title:
The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target.
Authors:
Donner, Jannik; Reck, Michael; Bergmann, Simone; Kirschning, Andreas; Müller, Rolf; Wagner-Döbler, Irene
Abstract:
New antibacterial compounds, preferentially exploiting novel cellular targets, are urgently needed to fight the increasing resistance of pathogens against conventional antibiotics. Here we demonstrate that Carolacton, a myxobacterial secondary metabolite previously shown to damage Streptococcus mutans biofilms, inhibits planktonic growth of Streptococcus pneumoniae TIGR4 and multidrug-resistant clinical isolates of serotype 19A at nanomolar concentrations. A Carolacton diastereomer is inactive in both streptococci, indicating a highly specific interaction with a conserved cellular target. S. mutans requires the eukaryotic-like serine/threonine protein kinase PknB and the cysteine metabolism regulator CysR for susceptibility to Carolacton, whereas their homologues are not needed in S. pneumoniae, suggesting a specific function for S. mutans biofilms only. A bactericidal effect of Carolacton was observed for S. pneumoniae TIGR4, with a reduction of cell numbers by 3 log units. The clinical pneumonia isolate Sp49 showed immediate growth arrest and cell lysis, suggesting a bacteriolytic effect of Carolacton. Carolacton treatment caused a reduction in membrane potential, but not membrane integrity, and transcriptome analysis revealed compensatory reactions of the cell. Our data show that Carolacton might have potential for treating pneumococcal infections.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target. 2016, 6:29677 Sci Rep
Journal:
Scientific reports
Issue Date:
2016
URI:
http://hdl.handle.net/10033/617011
DOI:
10.1038/srep29677
PubMed ID:
27404808
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
collections of the research group microbial communication (KOM)

Full metadata record

DC FieldValue Language
dc.contributor.authorDonner, Janniken
dc.contributor.authorReck, Michaelen
dc.contributor.authorBergmann, Simoneen
dc.contributor.authorKirschning, Andreasen
dc.contributor.authorMüller, Rolfen
dc.contributor.authorWagner-Döbler, Ireneen
dc.date.accessioned2016-07-15T14:02:35Z-
dc.date.available2016-07-15T14:02:35Z-
dc.date.issued2016-
dc.identifier.citationThe biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target. 2016, 6:29677 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid27404808-
dc.identifier.doi10.1038/srep29677-
dc.identifier.urihttp://hdl.handle.net/10033/617011-
dc.description.abstractNew antibacterial compounds, preferentially exploiting novel cellular targets, are urgently needed to fight the increasing resistance of pathogens against conventional antibiotics. Here we demonstrate that Carolacton, a myxobacterial secondary metabolite previously shown to damage Streptococcus mutans biofilms, inhibits planktonic growth of Streptococcus pneumoniae TIGR4 and multidrug-resistant clinical isolates of serotype 19A at nanomolar concentrations. A Carolacton diastereomer is inactive in both streptococci, indicating a highly specific interaction with a conserved cellular target. S. mutans requires the eukaryotic-like serine/threonine protein kinase PknB and the cysteine metabolism regulator CysR for susceptibility to Carolacton, whereas their homologues are not needed in S. pneumoniae, suggesting a specific function for S. mutans biofilms only. A bactericidal effect of Carolacton was observed for S. pneumoniae TIGR4, with a reduction of cell numbers by 3 log units. The clinical pneumonia isolate Sp49 showed immediate growth arrest and cell lysis, suggesting a bacteriolytic effect of Carolacton. Carolacton treatment caused a reduction in membrane potential, but not membrane integrity, and transcriptome analysis revealed compensatory reactions of the cell. Our data show that Carolacton might have potential for treating pneumococcal infections.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleThe biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalScientific reportsen

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