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Here we demonstrate that Carolacton, a myxobacterial secondary metabolite previously shown to damage <jats:italic>Streptococcus mutans<\/jats:italic> biofilms, inhibits planktonic growth of <jats:italic>Streptococcus pneumoniae<\/jats:italic> 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. <jats:italic>S. mutans<\/jats:italic> 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 <jats:italic>S. pneumoniae<\/jats:italic>, suggesting a specific function for <jats:italic>S. mutans<\/jats:italic> biofilms only. A bactericidal effect of Carolacton was observed for <jats:italic>S. pneumoniae<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/srep29677","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T13:25:39Z","timestamp":1468329939000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target"],"prefix":"10.1038","volume":"6","author":[{"given":"Jannik","family":"Donner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Reck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Bergmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Kirschning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Wagner-D\u00f6bler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,7,11]]},"reference":[{"key":"BFsrep29677_CR1","unstructured":"World Health Organization. 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