Format

Send to

Choose Destination
Int J Med Microbiol. 2014 Nov;304(8):931-40. doi: 10.1016/j.ijmm.2014.05.008. Epub 2014 May 28.

Metabolic and transcriptional activities of Staphylococcus aureus challenged with high-doses of daptomycin.

Author information

1
Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Lehrbereich Mikrobielle Genetik, Waldhäuser Str. 70/8, Eberhard Karls Universität Tübingen, 72076 Tübingen, Germany.
2
Lehrstuhl für Biochemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
3
Zentrum für Bioinformatik, Forschungsgruppe Integrative Transkriptomik, Eberhard Karls Universität Tübingen, Sand 14, 72076 Tübingen, Germany.
4
Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Lehrbereich Mikrobielle Genetik, Waldhäuser Str. 70/8, Eberhard Karls Universität Tübingen, 72076 Tübingen, Germany. Electronic address: ralph.bertram@uni-tuebingen.de.

Abstract

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 (13)C-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.

KEYWORDS:

Daptomycin; Drug tolerance; Persisters; Staphylococcus aureus

PMID:
24980509
DOI:
10.1016/j.ijmm.2014.05.008
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center