Sianglum, W;
Srimanote, P;
Taylor, PW;
Rosado, H;
Voravuthikunchai, SP;
(2012)
Transcriptome Analysis of Responses to Rhodomyrtone in Methicillin-Resistant Staphylococcus aureus.
PLOS ONE
, 7
(9)
, Article e45744. 10.1371/journal.pone.0045744.
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Abstract
Rhodomyrtone, purified from Rhodomyrtus tomentosa (Aiton) Hassk, exhibits a high degree of potency against methicillin-resistant Staphylococcus aureus (MRSA). We recently demonstrated that exposure of MRSA to a subinhibitory concentration (0.174 µg/ml) of rhodomyrtone resulted in the alteration of expression of several functional classes of bacterial proteins. To provide further insight into the antibacterial mode of action of this compound, we determined the impact of exposure to rhodomyrtone on the gene transcriptional profile of MRSA using microarray analysis. Exposure of MRSA to subinhibitory concentrations (0.5MIC; 0.5 µg/ml) of rhodomyrtone revealed significant modulation of gene expression, with induction of 64 genes and repression of 35 genes. Prominent changes in response to exposure to rhodomyrtone involved genes encoding proteins essential to metabolic pathways and processes such as amino acid metabolism, membrane function, ATP-binding cassette (ABC) transportation and lipoprotein and nucleotide metabolism. Genes involved in the synthesis of the aspartate family of amino acids, in particular proteins encoded by the dap operon were prominent. The diaminopimelate (DAP) biosynthetic pathway is the precursor of lysine synthesis and is essential for peptidoglycan biosynthesis. However, phenotypic analysis of the peptidoglycan amino acid content of rhodomyrtone-treated MRSA did not differ significantly from that extracted from control cells. Genes involved in the biosynthesis of amino acids and peptidoglycan, and a high affinity ATP-driven K (+) transport system, were investigated by quantitative reverse transcription-PCR (qRT-PCR) using EMRSA-16 1, 4, or 18 h after exposure to rhodomyrtone and in general the data concurred with that obtained by microarray, highlighting the relevance of the DAP biosynthetic pathway to the mode of action of rhodomyrtone.
| Type: | Article |
|---|---|
| Title: | Transcriptome Analysis of Responses to Rhodomyrtone in Methicillin-Resistant Staphylococcus aureus |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0045744 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0045744 |
| Additional information: | © Sianglum et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission (http://www.nru.psu.ac.th/) and the Thailand Research Fund through the Royal Golden Jubilee (RGJ) PhD program (http://rgj.trf.or.th/eng/rgje11.asp), grant no. PHD/0053/2550. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1373885 |
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