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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
Donner, Jannik
Reck, Michael
Bergmann, Simone
Kirschning, Andreas
Müller, Rolf
Wagner-Döbler, Irene
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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.
Citation
The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target. 2016, 6:29677 Sci Rep
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en
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2045-2322