Journal
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY
Volume 304, Issue 8, Pages 931-940Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.ijmm.2014.05.008
Keywords
Staphylococcus aureus; Daptomycin; Drug tolerance; Persisters
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Funding
- German Federal Ministry of Economics and Technology [KF2701103BZ1]
- priority program 1316 host adapted metabolism of bacterial pathogens [BE4038/2, EI384/5-2]
- Graduate College 685 Infection biology
- human- and plant-pathogenic bacteria and fungi of the Deutsche Forschungsgemeinschaft
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Treatment of stationary growth phase Staphylococcus aureus SA113 with 100-fold of the MIC of the lipopeptide antibiotic daptomycin leaves alive a small fraction of drug tolerant albeit genetically susceptible bacteria. This study shows that cells of this subpopulation exhibit active metabolism even hours after the onset of the drug challenge. Isotopologue profiling using fully C-13-labeled glucose revealed de novo biosynthesis of the amino acids Ala, Asp, Glu, Ser, Gly and His. The isotopologue composition in Asp and Glu suggested an increased activity of the TCA cycle under daptomycin treatment compared to unaffected stationary growth phase cells. Microarray analysis showed differential expression of specific genes 10 min and 3 h after addition of the drug. Besides factors involved in drug response, a number of metabolic genes appear to shape the signature of daptomycin-tolerant S. aureus cells. These observations will be useful toward the development of new strategies against persisters and related forms of bacterial cells with downshifted physiology. (C) 2014 Elsevier GmbH. All rights reserved.
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