Volume 208, Issue 2 pp. 203-206

The effect of antibiotic treatment on the intracellular nucleotide pools of Staphylococcus aureus

Rebecca C Greenwood

Rebecca C Greenwood

GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, PA, 19426-0989 USA

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Daniel R Gentry

Corresponding Author

Daniel R Gentry

GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, PA, 19426-0989 USA

*Corresponding author. Tel.: +1 (610) 917 7504; Fax: +1 (610) 917 7901, E-mail: [email protected]Search for more papers by this author
First published: 09 January 2006
Citations: 1

Abstract

In an assessment of antibiotic action on Staphylococcus aureus, we found that distinct changes in intracellular nucleotide pools occur depending on the antibiotic mode of action. In particular, we have quantitated the effect of antibiotics on pools of the nucleotide guanosine 3′-diphosphate, 5′-triphosphate (pppGpp). Intracellular pppGpp levels increased in response to treatment with the isoleucyl tRNA synthetase inhibitor mupirocin, the uncoupler carbonyl cyanide-m-chlorophenylhydrazone, and rifampicin. These compounds were distinguishable by the degree in which they increased the pppGpp pool and by their differential effect on the pools of other nucleotides. This technique has been used to confirm and to refute the expected mode of action of several compounds identified as possible inhibitors of tRNA synthetases. Our results provide the framework for using nucleotide analysis in the assessment of novel antimicrobial compounds with unknown modes of action.

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