title: Glucose Augments Killing Efficiency of Daptomycin Challenged Staphylococcus aureus Persisters.
abstract: Treatment of Staphylococcus aureus in stationary growth phase with high doses of the antibiotic daptomycin (DAP) eradicates the vast majority of the culture and leaves persister cells behind. Despite resting in a drug-tolerant and dormant state, persister cells exhibit metabolic activity which might be exploited for their elimination. We here report that the addition of glucose to S. aureus persisters treated with DAP increased killing by up to five-fold within one hour. This glucose-DAP effect also occurred with strains less sensitive to the drug. The underlying mechanism is independent of the proton motive force and was not observed with non-metabolizable 2-deoxy-glucose. Our results are consistent with two hypotheses on the glucose-DAP interplay. The first is based upon glucose-induced carbohydrate transport proteins that may influence DAP and the second suggests that glucose may trigger the release or activity of cell-lytic proteins to augment DAP's mode of action.
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Lehrbereich Mikrobielle Genetik, Auf der Morgenstelle 28, Eberhard Karls Universität Tübingen, 72076 Tübingen, Germany.|Paul-Ehrlich-Institut, Mikrobiologische Sicherheit, Paul-Ehrlich-Str. 51-59, 63225 Langen, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Prax
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Lehrbereich Mikrobielle Genetik, Auf der Morgenstelle 28, Eberhard Karls Universität Tübingen, 72076 Tübingen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Mechler
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Medizinische Mikrobiologie und Hygiene, Elfriede-Aulhorn-Str. 6, Eberhard Karls Universität Tübingen, 72076 Tübingen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Weidenmaier
authors.affiliation: Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Lehrbereich Mikrobielle Genetik, Auf der Morgenstelle 28, Eberhard Karls Universität Tübingen, 72076 Tübingen, Germany.|Klinikum Nürnberg Medical School GmbH, Research Department, Paracelsus Medical University, Nuremberg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Bertram
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D005947:Glucose; D017576:Daptomycin