Glucose Augments Killing Efficiency of Daptomycin Challenged Staphylococcus aureus Persisters

PLoS One. 2016 Mar 9;11(3):e0150907. doi: 10.1371/journal.pone.0150907. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Daptomycin / pharmacology*
  • Drug Synergism
  • Glucose / pharmacology*
  • Microbial Sensitivity Tests
  • Staphylococcus aureus / drug effects*

Substances

  • Anti-Bacterial Agents
  • Glucose
  • Daptomycin

Grant support

This work was supported by grant BE4038/2 within the priority programme 1316 “host adapted metabolism of bacterial pathogens” of the Deutsche Forschungsgemeinschaft (www.dfg.de). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.