Donner, Jannik; Reck, Michael; Bergmann, Simone; Kirschning, Andreas; Muller, Rolf; Wagner-Dobler, Irene: The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target. In: Scientific Reports 6 (2016), 29677. DOI: http://dx.doi.org/10.1038/srep29677
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. | |
License of this version: | CC BY 4.0 Unported |
Document Type: | Article |
Publishing status: | publishedVersion |
Issue Date: | 2016 |
Appears in Collections: | Naturwissenschaftliche Fakultät |
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