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

Donner, Jannik; Reck, Michael; Bergmann, Simone; Kirschning, Andreas; Müller, Rolf; Wagner-Döbler, Irene

dc.contributor.author	Donner, Jannik
dc.contributor.author	Reck, Michael
dc.contributor.author	Bergmann, Simone
dc.contributor.author	Kirschning, Andreas
dc.contributor.author	Müller, Rolf
dc.contributor.author	Wagner-Döbler, Irene
dc.date.accessioned	2016-07-15T14:02:35Z
dc.date.available	2016-07-15T14:02:35Z
dc.date.issued	2016
dc.identifier.citation	The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target. 2016, 6:29677 Sci Rep	en
dc.identifier.issn	2045-2322
dc.identifier.pmid	27404808
dc.identifier.doi	10.1038/srep29677
dc.identifier.uri	http://hdl.handle.net/10033/617011
dc.description.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.
dc.language.iso	en	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-sa/4.0/	*
dc.title	The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target.	en
dc.type	Article	en
dc.contributor.department	Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.	en
dc.identifier.journal	Scientific reports	en
refterms.dateFOA	2018-06-13T01:34:08Z
html.description.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.